The Experts below are selected from a list of 252 Experts worldwide ranked by ideXlab platform
Eugene C Butcher - One of the best experts on this subject based on the ideXlab platform.
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rotavirus specific b cells induced by recent infection in adults and children predominantly express the intestinal Homing Receptor α4β7
Virology, 2003Co-Authors: Ana Maria Gonzalez, Eugene C Butcher, Harry B Greenberg, Maria C Jaimes, Isabela Cajiao, Olga Lucia Rojas, Jean Cohen, Pierre Pothier, Evelyne Kohli, Juana AngelAbstract:Abstract In vivo replication of rotaviruses is generally limited to enterocytes. Because of this restriction, most blood circulating rotavirus-specific B cells are hypothesized to originate in Peyer's patches and should express the intestinal Homing Receptor α4β7. To test this hypothesis in humans, we used a flow cytometry assay that identifies antigen-activated (IgD−) B cells (CD19 + ) that express surface rotavirus-specific immunoglobulin. With this assay we could detect rotavirus-specific B cells in both children and adults with an acute rotavirus (RV) infection. Staining with an anti-α4β7 monoclonal antibody, we could determine that B cells that express rotavirus-specific surface immunoglobulin predominantly express α4β7. The response of rotavirus-specific antibody-secreting cells in the peripheral blood of children and adults with acute rotavirus infection was also studied by ELISPOT. The antibody-secreting cells of children were mainly of the IgM isotype, while the antibody-secreting cells of adults were predominantly of the IgA and IgG isotype. α4β7+ and α4β7− subsets of peripheral blood mononuclear cells were purified using paramagnetic beads and then tested in the ELISPOT assay. Rotavirus-specific antibody-secreting cells were predominantly present in the α4β7+ subpopulation. The flow cytometry assay we have described will permit future studies to characterize the phenotype of virus-specific B cells and could be useful in the study of the immunogenicity and protective efficacy of RV vaccines and the identification of markers of protective immunity.
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Rotavirus-specific B cells induced by recent infection in adults and children predominantly express the intestinal Homing Receptor alpha 4 beta 7
Virology, 2003Co-Authors: Ana Maria Gonzalez, Eugene C Butcher, Harry B Greenberg, Maria C Jaimes, Isabela Cajiao, Olga Lucia Rojas, Jean Cohen, Pierre Pothier, Evelyne Kohli, Juana AngelAbstract:In vivo replication of rotaviruses is generally limited to enterocytes. Because of this restriction, most blood circulating rotavirus-specific B cells are hypothesized to originate in Peyer's patches and should express the intestinal Homing Receptor alpha4beta7. To test this hypothesis in humans, we used a flow cytometry assay that identifies antigen-activated (IgD-) B cells (CD19(+)) that express surface rotavirus-specific immunoglobulin. With this assay we could detect rotavirus-specific B cells in both children and adults with an acute rotavirus (RV) infection. Staining with an anti-alpha4beta7 monoclonal antibody, we could determine that B cells that express rotavirus-specific surface immunoglobulin predominantly express alpha4beta7. The response of rotavirus-specific antibody-secreting cells in the peripheral blood of children and adults with acute rotavirus infection was also studied by ELISPOT. The antibody-secreting cells of children were mainly of the IgM isotype, while the antibody-secreting cells of adults were predominantly of the IgA and IgG isotype. alpha4beta7+ and alpha4beta7- subsets of peripheral blood mononuclear cells were purified using paramagnetic beads and then tested in the ELISPOT assay. Rotavirus-specific antibody-secreting cells were predominantly present in the alpha4beta7+ subpopulation. The flow cytometry assay we have described will permit future studies to characterize the phenotype of virus-specific B cells and could be useful in the study of the immunogenicity and protective efficacy of RV vaccines and the identification of markers of protective immunity.
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correlation of tissue distribution developmental phenotype and intestinal Homing Receptor expression of antigen specific b cells during the murine anti rotavirus immune response
Journal of Immunology, 2002Co-Authors: Kenneth R Youngman, Lusijah Rott, Eugene C Butcher, Manuel A Franco, Nelly A Kuklin, Harry B GreenbergAbstract:The intestinal Homing Receptor, alpha(4)beta(7), helps target lymphocytes to Peyer's patches (PP) and intestinal lamina propria (ILP). We have previously shown that protective immunity to rotavirus (RV), an intestinal pathogen, resides in memory B cells expressing alpha(4)beta(7). In this study, using a novel FACS assay, we have directly studied the phenotype of B cells that express surface RV-specific Ig during the in vivo RV immune response. During primary infection, RV-specific B cells first appear as large IgD(-)B220(low)alpha(4)beta(7)(-)and alpha(4)beta(7)(+) cells (presumptive extrafollicular, Ab-secreting B cells), and then as large and small IgD(-)B220(high)alpha(4)beta(7)(-)cells (presumptive germinal center B cells). The appearance of B cells with the phenotype of large IgD(-)B220(low)alpha(4)beta(7)(+) cells in PP and most notably in mesenteric lymph nodes coincides with the emergence of RV-specific Ab-secreting cells (ASC) in the ILP. Thus, these B lymphocytes are good candidates for the migratory population giving rise to the RV-specific ASC in the ILP. RV-specific long-term memory B cells preferentially accumulate in PP and express alpha(4)beta(7). Nine months after infection most RV-specific IgA ASC are found in PP and ILP and at lower frequency in bone marrow and spleen. This study is the first to follow changes in tissue-specific Homing Receptor expression during Ag-specific B cell development in response to a natural host, tissue-specific pathogen. These results show that alpha(4)beta(7) is tightly regulated during the Ag-specific B cell response to RV and is expressed concurrently with the specific migration of memory and effector B cells to intestinal tissues.
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the memory b cell subset responsible for the secretory iga response and protective humoral immunity to rotavirus expresses the intestinal Homing Receptor α4β7
Journal of Immunology, 1998Co-Authors: Marna Williams, Lusijah Rott, Manuel A Franco, Harry B Greenberg, Jason R Rose, Eugene C ButcherAbstract:Infection of mice with murine rotaviruses induces life-long immunity, characterized by high levels of IgA in the intestine and large numbers of rotavirus (RV)-specific Ab-secreting cells in gut-associated lymphoid tissues. Lymphocyte trafficking into gut-associated lymphoid tissues is mediated by interaction of the α4β7 integrin on lymphocytes with the vascular mucosal addressin cell adhesion molecule-1. To determine whether B cell memory for RV correlates with α4β7 expression, we transferred sorted B220+ phenotypically defined memory (IgD−α4β7high and IgD− α4β7−) and naive (IgD+α4β7+) splenocytes into recombination-activating gene-2 knockout mice (B and T cell-deficient) that were chronically infected with RV. Only mice receiving α4β7high memory (IgD−) B cells produced RV-specific IgA in the stool, cleared the virus, and were immune to reinfection. α4β7high (but not α4β7−) memory B cells from donors boosted as much as 7 mo previously also cleared the virus, indicating that α4β7high memory B cells maintain long term functional immunity to RV. Although only α4β7high memory cells provided mucosal immunity, α4β7− cells from recently boosted donor animals could generate RV-specific serum IgG, but, like naive (IgD+) B cells, were unable to induce viral clearance even 60 days after cell transfer. These data indicate that protective immunity for an intestinal pathogen, RV, resides in memory phenotype B cells expressing the intestinal Homing Receptor, α4β7.
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expression of the mucosal Homing Receptor α4β7 correlates with the ability of cd8 memory t cells to clear rotavirus infection
Journal of Virology, 1998Co-Authors: Jason R Rose, Lusijah Rott, Eugene C Butcher, Marna Williams, Harry B GreenbergAbstract:The integrin α4β7 plays an important role in lymphocyte Homing to mucosal lymphoid tissues and has been shown to define a subpopulation of memory T cells capable of Homing to intestinal sites. Here we have used a well-characterized intestinal virus, murine rotavirus, to investigate whether memory/effector function for an intestinal pathogen is associated with α4β7 expression. α4β7hi memory phenotype (CD44hi), α4β7− memory phenotype, and presumptively naive (CD44lo) CD8+ T lymphocytes from rotavirus-infected mice were sorted and transferred into Rag-2 (T- and B-cell-deficient) recipients that were chronically infected with murine rotavirus. α4β7hi memory phenotype CD8+ cells were highly efficient at clearing rotavirus infection, α4β7− memory cells were inefficient or ineffective, depending on the cell numbers transferred, and CD44lo cells were completely unable to clear chronic rotavirus infection. These data demonstrate that functional memory for rotavirus resides primarily in memory phenotype cells that display the mucosal Homing Receptor α4β7.
Harry B Greenberg - One of the best experts on this subject based on the ideXlab platform.
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Human rotavirus specific T cells: quantification by ELISPOT and expression of Homing Receptors on CD4+ T cells
Virology, 2003Co-Authors: Olga Lucia Rojas, Manuel A Franco, Harry B Greenberg, Ana Maria Gonzalez, Rosabel González, Irene Pérez-schael, Juana AngelAbstract:Using an intracellular cytokine assay, we recently showed that the frequencies of rotavirus (RV)-specific CD4(+) and CD8(+) T cells secreting INFgamma, circulating in RV infected and healthy adults, are very low compared to the frequencies of circulating cytomegalovirus (CMV) reactive T cells in comparable individuals. In children with acute RV infection, these T cells were barely or not detectable. In the present study, an ELISPOT assay enabled detection of circulating RV-specific INFgamma-secreting cells in children with RV diarrhea but not in children with non-RV diarrhea without evidence of a previous RV infection. Using microbead-enriched CD4(+) and CD8(+) T cell subsets, IFNgamma-secreting RV-specific CD8(+) but not CD4(+) T cells were detected in recently infected children. Using the same approach, both CD4(+) and CD8(+) RV-specific T cells were detected in healthy adults. Furthermore, stimulation of purified subsets of PBMC that express lymphocyte Homing Receptors demonstrated that RV-specific INFgamma-secreting CD4(+) T cells from adult volunteers preferentially express the intestinal Homing Receptor alpha4beta7, but not the peripheral lymph node Homing Receptor L-selectin. In contrast, CMV-specific INFgamma-secreting CD4(+) T cells preferentially express L-selectin but not alpha4beta7. These results suggest that the expression of Homing Receptors on virus-specific T cells depends on the organ where these cells were originally stimulated and that their capacity to secrete INFgamma is independent of the expression of these Homing Receptors.
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rotavirus specific b cells induced by recent infection in adults and children predominantly express the intestinal Homing Receptor α4β7
Virology, 2003Co-Authors: Ana Maria Gonzalez, Eugene C Butcher, Harry B Greenberg, Maria C Jaimes, Isabela Cajiao, Olga Lucia Rojas, Jean Cohen, Pierre Pothier, Evelyne Kohli, Juana AngelAbstract:Abstract In vivo replication of rotaviruses is generally limited to enterocytes. Because of this restriction, most blood circulating rotavirus-specific B cells are hypothesized to originate in Peyer's patches and should express the intestinal Homing Receptor α4β7. To test this hypothesis in humans, we used a flow cytometry assay that identifies antigen-activated (IgD−) B cells (CD19 + ) that express surface rotavirus-specific immunoglobulin. With this assay we could detect rotavirus-specific B cells in both children and adults with an acute rotavirus (RV) infection. Staining with an anti-α4β7 monoclonal antibody, we could determine that B cells that express rotavirus-specific surface immunoglobulin predominantly express α4β7. The response of rotavirus-specific antibody-secreting cells in the peripheral blood of children and adults with acute rotavirus infection was also studied by ELISPOT. The antibody-secreting cells of children were mainly of the IgM isotype, while the antibody-secreting cells of adults were predominantly of the IgA and IgG isotype. α4β7+ and α4β7− subsets of peripheral blood mononuclear cells were purified using paramagnetic beads and then tested in the ELISPOT assay. Rotavirus-specific antibody-secreting cells were predominantly present in the α4β7+ subpopulation. The flow cytometry assay we have described will permit future studies to characterize the phenotype of virus-specific B cells and could be useful in the study of the immunogenicity and protective efficacy of RV vaccines and the identification of markers of protective immunity.
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Rotavirus-specific B cells induced by recent infection in adults and children predominantly express the intestinal Homing Receptor alpha 4 beta 7
Virology, 2003Co-Authors: Ana Maria Gonzalez, Eugene C Butcher, Harry B Greenberg, Maria C Jaimes, Isabela Cajiao, Olga Lucia Rojas, Jean Cohen, Pierre Pothier, Evelyne Kohli, Juana AngelAbstract:In vivo replication of rotaviruses is generally limited to enterocytes. Because of this restriction, most blood circulating rotavirus-specific B cells are hypothesized to originate in Peyer's patches and should express the intestinal Homing Receptor alpha4beta7. To test this hypothesis in humans, we used a flow cytometry assay that identifies antigen-activated (IgD-) B cells (CD19(+)) that express surface rotavirus-specific immunoglobulin. With this assay we could detect rotavirus-specific B cells in both children and adults with an acute rotavirus (RV) infection. Staining with an anti-alpha4beta7 monoclonal antibody, we could determine that B cells that express rotavirus-specific surface immunoglobulin predominantly express alpha4beta7. The response of rotavirus-specific antibody-secreting cells in the peripheral blood of children and adults with acute rotavirus infection was also studied by ELISPOT. The antibody-secreting cells of children were mainly of the IgM isotype, while the antibody-secreting cells of adults were predominantly of the IgA and IgG isotype. alpha4beta7+ and alpha4beta7- subsets of peripheral blood mononuclear cells were purified using paramagnetic beads and then tested in the ELISPOT assay. Rotavirus-specific antibody-secreting cells were predominantly present in the alpha4beta7+ subpopulation. The flow cytometry assay we have described will permit future studies to characterize the phenotype of virus-specific B cells and could be useful in the study of the immunogenicity and protective efficacy of RV vaccines and the identification of markers of protective immunity.
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correlation of tissue distribution developmental phenotype and intestinal Homing Receptor expression of antigen specific b cells during the murine anti rotavirus immune response
Journal of Immunology, 2002Co-Authors: Kenneth R Youngman, Lusijah Rott, Eugene C Butcher, Manuel A Franco, Nelly A Kuklin, Harry B GreenbergAbstract:The intestinal Homing Receptor, alpha(4)beta(7), helps target lymphocytes to Peyer's patches (PP) and intestinal lamina propria (ILP). We have previously shown that protective immunity to rotavirus (RV), an intestinal pathogen, resides in memory B cells expressing alpha(4)beta(7). In this study, using a novel FACS assay, we have directly studied the phenotype of B cells that express surface RV-specific Ig during the in vivo RV immune response. During primary infection, RV-specific B cells first appear as large IgD(-)B220(low)alpha(4)beta(7)(-)and alpha(4)beta(7)(+) cells (presumptive extrafollicular, Ab-secreting B cells), and then as large and small IgD(-)B220(high)alpha(4)beta(7)(-)cells (presumptive germinal center B cells). The appearance of B cells with the phenotype of large IgD(-)B220(low)alpha(4)beta(7)(+) cells in PP and most notably in mesenteric lymph nodes coincides with the emergence of RV-specific Ab-secreting cells (ASC) in the ILP. Thus, these B lymphocytes are good candidates for the migratory population giving rise to the RV-specific ASC in the ILP. RV-specific long-term memory B cells preferentially accumulate in PP and express alpha(4)beta(7). Nine months after infection most RV-specific IgA ASC are found in PP and ILP and at lower frequency in bone marrow and spleen. This study is the first to follow changes in tissue-specific Homing Receptor expression during Ag-specific B cell development in response to a natural host, tissue-specific pathogen. These results show that alpha(4)beta(7) is tightly regulated during the Ag-specific B cell response to RV and is expressed concurrently with the specific migration of memory and effector B cells to intestinal tissues.
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the memory b cell subset responsible for the secretory iga response and protective humoral immunity to rotavirus expresses the intestinal Homing Receptor α4β7
Journal of Immunology, 1998Co-Authors: Marna Williams, Lusijah Rott, Manuel A Franco, Harry B Greenberg, Jason R Rose, Eugene C ButcherAbstract:Infection of mice with murine rotaviruses induces life-long immunity, characterized by high levels of IgA in the intestine and large numbers of rotavirus (RV)-specific Ab-secreting cells in gut-associated lymphoid tissues. Lymphocyte trafficking into gut-associated lymphoid tissues is mediated by interaction of the α4β7 integrin on lymphocytes with the vascular mucosal addressin cell adhesion molecule-1. To determine whether B cell memory for RV correlates with α4β7 expression, we transferred sorted B220+ phenotypically defined memory (IgD−α4β7high and IgD− α4β7−) and naive (IgD+α4β7+) splenocytes into recombination-activating gene-2 knockout mice (B and T cell-deficient) that were chronically infected with RV. Only mice receiving α4β7high memory (IgD−) B cells produced RV-specific IgA in the stool, cleared the virus, and were immune to reinfection. α4β7high (but not α4β7−) memory B cells from donors boosted as much as 7 mo previously also cleared the virus, indicating that α4β7high memory B cells maintain long term functional immunity to RV. Although only α4β7high memory cells provided mucosal immunity, α4β7− cells from recently boosted donor animals could generate RV-specific serum IgG, but, like naive (IgD+) B cells, were unable to induce viral clearance even 60 days after cell transfer. These data indicate that protective immunity for an intestinal pathogen, RV, resides in memory phenotype B cells expressing the intestinal Homing Receptor, α4β7.
Louis J Picker - One of the best experts on this subject based on the ideXlab platform.
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independent regulation of cutaneous lymphocyte associated antigen expression and cytokine synthesis phenotype during human cd4 memory t cell differentiation
Journal of Immunology, 1997Co-Authors: Yuichi Teraki, Louis J PickerAbstract:Although considerable attention has been paid to the development of cytokine synthesis heterogeneity during memory T cell differentiation, little information is available on how this function is coregulated with Homing Receptor expression. The development of skin-Homing, CD4+ memory T cells in the human provides an excellent model for such investigation, since 1) the skin supports both Th1- and Th2-predominant responses in different settings, and 2) the skin-Homing capability of human memory T cells correlates with and appears to depend on expression of the skin-selective Homing Receptor cutaneous lymphocyte-associated Ag (CLA). In this study, we used multiparameter FACS analysis to examine expression of CLA vs IFN-gamma, IL-4, and IL-2 synthesis capabilities among fresh peripheral blood CD4+ memory T cells, and Th1 vs Th2 memory T cells generated in vitro from purified CD4+ naive precursors by cyclic activation in polarizing culture conditions. Among normal peripheral blood T cells, CLA expression was essentially identical among the IFN-gamma- vs IL-4-producing CD4+ memory subsets, clearly indicating the existence of in vivo mechanisms capable of producing both Th1 vs Th2 skin-Homing T cells. In vitro differentiation of naive CD4+ T cells confirmed the independent regulation of CLA and all three cytokines examined, regulation that allowed differential production of IFN-gamma-, IL-4-, and IL-2-producing, CLA+ memory subsets. These studies also 1) demonstrated differences in regulatory factor activity depending on the differentiation status of the responding cell, and 2) revealed CLA expression to be much more rapidly reversible on established memory cells than cytokine synthesis capabilities.
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bacterial superantigens induce t cell expression of the skin selective Homing Receptor the cutaneous lymphocyte associated antigen via stimulation of interleukin 12 production
Journal of Experimental Medicine, 1995Co-Authors: Donald Y M Leung, Maurice K Gately, Anne E Trumble, Bonnie Fergusondarnell, Patrick M Schlievert, Louis J PickerAbstract:T lymphocyte infiltration is a prominent feature of the skin inflammation associated with infections by toxin (superantigen)-secreting Staphylococcus aureus or Streptococcus bacteria. The cutaneous lymphocyte-associated antigen (CLA) has been hypothesized to be a Homing Receptor (HR) involved in selective migration of memory/effector T cells to the skin. Since the expression of this putative skin-selective HR is known to be under strict microenvironmental control, we sought to determine the effect of staphylococcal and streptococcal toxins on T cell expression of CLA. After in vitro stimulation of peripheral blood mononuclear cells with staphylococcal enterotoxin B, toxic shock syndrome toxin-1, and streptococcal pyrogenic exotoxins A and C, there was a significant increase in the numbers of CLA+ T cell blasts (p < 0.01), but not blasts bearing the mucosa-associated adhesion molecule alpha e beta 7-integrin, compared with T cells stimulated with phytohemaglutinin (PHA) or anti-CD3. Bacterial toxins were also found to specifically induce interleukin (IL) 12 production. More importantly, induction of toxin-induced CLA expression was blocked by anti-IL-12, and the addition of IL-12 to PHA-stimulated T cells induced CLA, but not alpha e beta 7-integrin, expression. These data suggest that bacterial toxins induce the expansion of skin-Homing CLA+ T cells in an IL-12-dependent manner, and thus may contribute to the development of skin rashes in superantigen-mediated diseases.
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the human peripheral lymph node vascular addressin an inducible endothelial antigen involved in lymphocyte Homing
American Journal of Pathology, 1993Co-Authors: Sara A. Michie, Eugene C Butcher, Philip R. Streeter, P A Bolt, Louis J PickerAbstract:The extravasation of blood-borne lymphocytes into organized lymphoid tissues and sites of chronic inflammation is directed in part by interactions of lymphocyte surface adhesion molecules, known as Homing Receptors, with tissue-selective endothelial ligands called vascular addressins. In mice and humans, lymphocyte L-selectin and the peripheral lymph node addressin (PNAd) form a Homing Receptor-endothelial ligand pair involved in lymphocyte traffic to peripheral lymph node (PLN). We have examined the tissue distribution and function of human PNAd, using monoclonal antibody MECA-79 and in vitro assays of L-selectin-dependent lymphocyte binding. We demonstrate that PNAd is expressed by human high endothelial venules (HEV) in lymphoid tissues which support lymphocyte adhesion via a PLN-associated recognition system. MECA-79 inhibits adhesion to these HEV of a cell line that binds predominantly via the PLN-Homing Receptor, L-selectin, but has no effect on adhesion by a mucosal HEV-binding cell line. Furthermore, MECA-79 blocks binding of human peripheral blood mononuclear cells to both PLN and tonsil HEV, but not significantly to HEV in the appendix. In addition, we demonstrate PNAd induction on venules at chronic inflammatory sites in humans, particularly sites with severe or long-standing chronic inflammatory involvement. These results confirm that PNAd functions as a PLN vascular addressin in humans, and that in addition to directing normal lymphocyte recirculation to lymph nodes and tonsils, this addressin likely participates in lymphocyte recruitment to sites of chronic inflammation.
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control of lymphocyte recirculation in man ii differential regulation of the cutaneous lymphocyte associated antigen a tissue selective Homing Receptor for skin Homing t cells
Journal of Immunology, 1993Co-Authors: Louis J Picker, J R Treer, B Fergusondarnell, P A Collins, Paul R Bergstresser, Leon W M M TerstappenAbstract:Recent work indicates that a novel Homing Receptor (HR)/endothelial ligand pair--the cutaneous lymphocyte-associated Ag (CLA) and E-selectin--is involved in targeting a unique skin-associated subpopulation of memory T cells to cutaneous sites of chronic inflammation. To investigate the regulatory mechanisms responsible for the generation of a memory T cell subset with skin-selective Homing capability, we used multiparameter flow cytometry to assess the expression of CLA on T cells during initial T cell activation in secondary lymphoid tissues (the virgin to memory transition), and upon reactivation in skin. Our analyses indicate that in vivo induction of CLA (and E-selectin-binding ability) first occurs during the virgin to memory transition, and is regulated in a highly tissue-selective manner. The frequency of CLA expression on CD45RA+/RO+ transitional T cells within skin-associated peripheral lymph nodes was > fivefold higher than within the mucosal microenvironment of the appendix. In keeping with its role as a skin-selective Homing Receptor, levels of cell-surface CLA on T cells obtained from cutaneous blisters overlying delayed-type hypersensitivity sites were a mean 23-fold higher than on corresponding peripheral blood T cells, including all time points of lesional evolution. However, comparisons of CLA expression on resting vs activated skin blister T cells (HLA-DR - vs +, respectively) indicated that CLA expression, which is already quite high on the resting subset, appeared to be further up-regulated upon activation in skin. The critical involvement of local microenvironments in the regulation of CLA expression was also supported by in vitro studies demonstrating the necessity of specific secondary signals for the induction of CLA glycoproteins on mitogen-activated T cells. CLA up-regulation on both the virgin and memory T cell subsets was dependent on the presence of TGF-beta 1 (or, to a lesser extent, IL-6), but not a wide variety of other cytokines. Thus, the development of the CLA+ memory T cell subset is likely a product of the cumulative experience of those T cells with respect to local microenvironments at previous sites of activation, perhaps involving differential availability of bioactive TGF-beta 1 and/or IL-6 (both cytokines produced in skin). Repeated activation in skin or skin-associated peripheral lymph nodes may act to reinforce CLA expression on T cells functionally-associated with skin, and thus enhance the functional efficiency of these cells by preferentially focusing their recirculation to the skin or related sites.
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control of lymphocyte recirculation in man i differential regulation of the peripheral lymph node Homing Receptor l selectin on t cells during the virgin to memory cell transition
Journal of Immunology, 1993Co-Authors: Louis J Picker, J R Treer, B Fergusondarnell, P A Collins, D Buck, Leon W M M TerstappenAbstract:Conventional virgin lymphocytes of a given class show relatively homogeneous recirculation through secondary lymphoid tissues, whereas memory/effector populations are composed of distinct subsets with differential, often tissue-selective migratory capability. In keeping with these observations, CD45RAhigh/ROlow "virgin" T cells in human peripheral blood uniformly express the peripheral lymph node Homing Receptor (HR) L-selectin, whereas among the CD45RAlow/ROhigh "memory/effector" subset, the expression of this HR is bimodal. To investigate the mechanisms responsible for the generation of memory/effector T cell subsets with differential Homing potential, we developed a multiparameter flow cytometric technique that defines a common pathway of post-thymic T cell differentiation in secondary lymphoid tissues. Our analyses indicate that the virgin to memory T cell transition is characterized by a stepwise, unidirectional progression through distinct CD45RA+/RO+ intermediates that allow the in vivo discrimination of early, middle, and late transitional T cells. In normal peripheral blood, few T cells with a transitional phenotype are identified, but in secondary lymphoid tissues, 2 to 10% of T cells have this phenotype, including those CD45RA+ T cells that 1) are morphologically blasts, 2) are in S or G2/M phase of the cell cycle, or 3) express activation Ag. General adhesion molecules (LFA-1, LFA-3, ICAM-1) are uniformly up-regulated concordant with changes in T cell expression of CD45RA/RO in all tissues examined. Early in the transition, L-selectin is also uniformly up-regulated, but in subsequent stages, T cell expression of this HR is preferentially down-regulated in mucosal lymphoid tissues, and retained in peripheral lymph node. Differential regulation of L-selectin can also be demonstrated in vitro by the activation of virgin T cells in the presence of specific cytokines--IL-2 induces L-selectin down-regulation, whereas IL-6 and particularly TGF-beta 1 promote L-selectin up-regulation. Taken together, these findings support the hypothesis that local microenvironments within particular secondary lymphoid tissues influence HR expression at the time of CD45RA/RO conversion, and thereby contribute to the formation of CD45RAlow/ROhigh memory/effector T cell populations with tissue-selective Homing behavior.
Leo Boneschansker - One of the best experts on this subject based on the ideXlab platform.
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subsets of human cd4 regulatory t cells express the peripheral Homing Receptor cxcr3
European Journal of Immunology, 2011Co-Authors: Andre Hoerning, Kerith Koss, Dipak Datta, Leo BoneschanskerAbstract:Regulatory T cells (Tregs) migrate into peripheral sites of inflammation such as allografts undergoing rejection, where they serve to suppress the immune response. In this study, we find that ∼30-40% of human CD25(hi) FOXP3(+) CD4(+) Tregs express the peripheral CXC chemokine Receptor 3 (CXCR3) and that this subset has potent immunoregulatory properties. Consistently, we observed that proliferative responses as well as IFN-γ production were significantly higher using CXCR3-depleted versus undepleted responders in the mixed lymphocyte reaction, as well as following mitogen-dependent activation of T cells. Using microfluidics, we also found that CXCR3 was functional on CXCR3(pos) Tregs, in as much as chemotaxis and directional persistence towards interferon-γ-inducible protein of 10 kDa (IP-10) was significantly greater for CXCR3(pos) than CXCR3(neg) Tregs. Following activation, CXCR3-expressing CD4(+) Tregs were maintained in vitro in cell culture in the presence of the mammalian target of rapamycin (mTOR) inhibitor rapamycin, and we detected higher numbers of circulating CXCR3(+) FOXP3(+) T cells in adult and pediatric recipients of renal transplants who were treated with mTOR-inhibitor immunosuppressive therapy. Collectively, these results demonstrate that the peripheral Homing Receptor CXCR3 is expressed on subset(s) of circulating human Tregs and suggest a role for CXCR3 in their recruitment into peripheral sites of inflammation.
Juana Angel - One of the best experts on this subject based on the ideXlab platform.
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Human rotavirus specific T cells: quantification by ELISPOT and expression of Homing Receptors on CD4+ T cells
Virology, 2003Co-Authors: Olga Lucia Rojas, Manuel A Franco, Harry B Greenberg, Ana Maria Gonzalez, Rosabel González, Irene Pérez-schael, Juana AngelAbstract:Using an intracellular cytokine assay, we recently showed that the frequencies of rotavirus (RV)-specific CD4(+) and CD8(+) T cells secreting INFgamma, circulating in RV infected and healthy adults, are very low compared to the frequencies of circulating cytomegalovirus (CMV) reactive T cells in comparable individuals. In children with acute RV infection, these T cells were barely or not detectable. In the present study, an ELISPOT assay enabled detection of circulating RV-specific INFgamma-secreting cells in children with RV diarrhea but not in children with non-RV diarrhea without evidence of a previous RV infection. Using microbead-enriched CD4(+) and CD8(+) T cell subsets, IFNgamma-secreting RV-specific CD8(+) but not CD4(+) T cells were detected in recently infected children. Using the same approach, both CD4(+) and CD8(+) RV-specific T cells were detected in healthy adults. Furthermore, stimulation of purified subsets of PBMC that express lymphocyte Homing Receptors demonstrated that RV-specific INFgamma-secreting CD4(+) T cells from adult volunteers preferentially express the intestinal Homing Receptor alpha4beta7, but not the peripheral lymph node Homing Receptor L-selectin. In contrast, CMV-specific INFgamma-secreting CD4(+) T cells preferentially express L-selectin but not alpha4beta7. These results suggest that the expression of Homing Receptors on virus-specific T cells depends on the organ where these cells were originally stimulated and that their capacity to secrete INFgamma is independent of the expression of these Homing Receptors.
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rotavirus specific b cells induced by recent infection in adults and children predominantly express the intestinal Homing Receptor α4β7
Virology, 2003Co-Authors: Ana Maria Gonzalez, Eugene C Butcher, Harry B Greenberg, Maria C Jaimes, Isabela Cajiao, Olga Lucia Rojas, Jean Cohen, Pierre Pothier, Evelyne Kohli, Juana AngelAbstract:Abstract In vivo replication of rotaviruses is generally limited to enterocytes. Because of this restriction, most blood circulating rotavirus-specific B cells are hypothesized to originate in Peyer's patches and should express the intestinal Homing Receptor α4β7. To test this hypothesis in humans, we used a flow cytometry assay that identifies antigen-activated (IgD−) B cells (CD19 + ) that express surface rotavirus-specific immunoglobulin. With this assay we could detect rotavirus-specific B cells in both children and adults with an acute rotavirus (RV) infection. Staining with an anti-α4β7 monoclonal antibody, we could determine that B cells that express rotavirus-specific surface immunoglobulin predominantly express α4β7. The response of rotavirus-specific antibody-secreting cells in the peripheral blood of children and adults with acute rotavirus infection was also studied by ELISPOT. The antibody-secreting cells of children were mainly of the IgM isotype, while the antibody-secreting cells of adults were predominantly of the IgA and IgG isotype. α4β7+ and α4β7− subsets of peripheral blood mononuclear cells were purified using paramagnetic beads and then tested in the ELISPOT assay. Rotavirus-specific antibody-secreting cells were predominantly present in the α4β7+ subpopulation. The flow cytometry assay we have described will permit future studies to characterize the phenotype of virus-specific B cells and could be useful in the study of the immunogenicity and protective efficacy of RV vaccines and the identification of markers of protective immunity.
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Rotavirus-specific B cells induced by recent infection in adults and children predominantly express the intestinal Homing Receptor alpha 4 beta 7
Virology, 2003Co-Authors: Ana Maria Gonzalez, Eugene C Butcher, Harry B Greenberg, Maria C Jaimes, Isabela Cajiao, Olga Lucia Rojas, Jean Cohen, Pierre Pothier, Evelyne Kohli, Juana AngelAbstract:In vivo replication of rotaviruses is generally limited to enterocytes. Because of this restriction, most blood circulating rotavirus-specific B cells are hypothesized to originate in Peyer's patches and should express the intestinal Homing Receptor alpha4beta7. To test this hypothesis in humans, we used a flow cytometry assay that identifies antigen-activated (IgD-) B cells (CD19(+)) that express surface rotavirus-specific immunoglobulin. With this assay we could detect rotavirus-specific B cells in both children and adults with an acute rotavirus (RV) infection. Staining with an anti-alpha4beta7 monoclonal antibody, we could determine that B cells that express rotavirus-specific surface immunoglobulin predominantly express alpha4beta7. The response of rotavirus-specific antibody-secreting cells in the peripheral blood of children and adults with acute rotavirus infection was also studied by ELISPOT. The antibody-secreting cells of children were mainly of the IgM isotype, while the antibody-secreting cells of adults were predominantly of the IgA and IgG isotype. alpha4beta7+ and alpha4beta7- subsets of peripheral blood mononuclear cells were purified using paramagnetic beads and then tested in the ELISPOT assay. Rotavirus-specific antibody-secreting cells were predominantly present in the alpha4beta7+ subpopulation. The flow cytometry assay we have described will permit future studies to characterize the phenotype of virus-specific B cells and could be useful in the study of the immunogenicity and protective efficacy of RV vaccines and the identification of markers of protective immunity.