The Experts below are selected from a list of 166536 Experts worldwide ranked by ideXlab platform
Philip E. Thorpe - One of the best experts on this subject based on the ideXlab platform.
-
Blocked and non-blocked ricin immunotoxins against the CD4 Antigen exhibit higher cytotoxic potency than a ricin A chain immunotoxin potentiated with ricin B chain or with a ricin B chain immunotoxin
Cancer Immunology Immunotherapy, 1991Co-Authors: Edward J. Wawrzynczak, Graham J. Watson, Alan J. Cumber, Raymond V. Henry, Geoffrey D. Parnell, E. Peter Rieber, Philip E. ThorpeAbstract:An immunotoxin consisting of ricin A chain linked to the monoclonal antibody M-T151, recognising the CD4 Antigen, was weakly toxic to the human T-lymphoblastoid cell line CEM in tissue culture. The incorporation of [^3H]leucine by CEM cells was inhibited by 50% at an M-T151-ricin-A-chain concentration (IC_50) of 4.6 nM compared with an IC_50 of 1.0 pM for ricin. In contrast, immunotoxins made by linking intact ricin to M-T151 in such a way that the galactose-binding sites of the B chain subunit were either blocked sterically by the antibody component or were left unblocked, were both powerfully cytotoxic with IC_50 values of 20–30 pM. The addition of ricin B chain to CEM cells treated with M-T151—ricin-A-chain enhanced cytotoxicity by only eight-fold indicating that isolated B chain potentiated the action of the A chain less effectively than it did as an integral component of an intact ricin immunotoxin. Ricin B chain linked to goat anti-(mouse immunoglobulin) also potentiated weakly. Lactose completely inhibited the ability of isolated ricin B chain to potentiate the cytotoxicity of M-T151—ricin-A-chain and partially (3- to 4-fold) inhibited the cytotoxicity of the blocked and non-blocked ricin immunotoxins. Thus, in this system, the galactose-binding sites of the B chain contributed to cell killing regardless of whether isolated B chain was associated with the A chain immunotoxin or was present in blocked or non-blocked form as part of an intact ricin immunotoxin. The findings suggest that the blocked ricin immunotoxin may become unblocked after binding to the target Antigen to re-expose the cryptic galactose-binding sites. However, the unblocking cannot be complete because the maximal inhibition of [^3H]leucine incorporation by the blocked immunotoxin was only 80% compared with greater than 99% inhibition by the non-blocked immunotoxin.
-
Blocked and non-blocked ricin immunotoxins against the CD4 Antigen exhibit higher cytotoxic potency than a ricin A chain immunotoxin potentiated with ricin B chain or with a ricin B chain immunotoxin.
Cancer Immunology Immunotherapy, 1991Co-Authors: Edward J. Wawrzynczak, Graham J. Watson, Alan J. Cumber, Raymond V. Henry, Geoffrey D. Parnell, E. Peter Rieber, Philip E. ThorpeAbstract:An immunotoxin consisting of ricin A chain linked to the monoclonal antibody M-T151, recognising the CD4 Antigen, was weakly toxic to the human T-lymphoblastoid cell line CEM in tissue culture. The incorporation of [3H]leucine by CEM cells was inhibited by 50% at an M-T151-ricin-A-chain concentration (IC50) of 4.6 nM compared with an IC50 of 1.0 pM for ricin. In contrast, immunotoxins made by linking intact ricin to M-T151 in such a way that the galactose-binding sites of the B chain subunit were either blocked sterically by the antibody component or were left unblocked, were both powerfully cytotoxic with IC50 values of 20–30 pM. The addition of ricin B chain to CEM cells treated with M-T151—ricin-A-chain enhanced cytotoxicity by only eight-fold indicating that isolated B chain potentiated the action of the A chain less effectively than it did as an integral component of an intact ricin immunotoxin. Ricin B chain linked to goat anti-(mouse immunoglobulin) also potentiated weakly.
Joël Mazurier - One of the best experts on this subject based on the ideXlab platform.
-
Lactoferrin upregulates the expression of CD4 Antigen through the stimulation of the mitogen-activated protein kinase in the human lymphoblastic T Jurkat cell line.
Journal of Cellular Biochemistry, 2000Co-Authors: Isabelle Dhennin‐duthille, Geneviève Spik, M. Masson, Eve Damiens, Carine Fillebeen, Joël MazurierAbstract:The main biological properties of lactoferrin are thought to concern inflammation and immunomodulation processes, including maturation of immature B and T cells. Lactoferrin accelerates T-cell maturation by inducing the expression of the CD4 surface marker. In this report, using the Jurkat T-cell line, we have shown that lactoferrin upregulates the expression of CD4 Antigen through the activation of a transduction pathway. Using an anti-phosphotyrosine antibody, lactoferrin was demonstrated to induce a cascade of phosphorylation of numerous proteins on their tyrosine residues. This tyrosine-phosphorylation was transient, reaching maxima between 5 and 10 min. We also identified the mitogen-activated protein kinase (MAP kinase) which presented an enhanced catalytic activity, reaching a maximum at 10 min of incubation with lactoferrin. Moreover, the use of inhibitors such as genistein and PD98059, tyrosine kinases and MAP kinase kinase (or MEK) inhibitors respectively, allowed us to correlate the activation of MAP kinase with the upregulation of CD4 expression. Finally, using Lck-defective Jurkat cells, our results showed that the p56lck (Lck) kinase is necessary for MAP kinase activity and CD4 expression. This paper demonstrates that lactoferrin activates transduction pathway(s) in lymphoblastic T-cells, and that Lck and the Erk2 isoform of MAP kinase are implicated in the upregulation of CD4, induced by lactoferrin in these cells. J. Cell. Biochem. 79:583–593, 2000. © 2000 Wiley-Liss, Inc.
-
Lactoferrin upregulates the expression of CD4 Antigen through the stimulation of the mitogen-activated protein kinase in the human lymphoblastic T Jurkat cell line.
Journal of Cellular Biochemistry, 2000Co-Authors: Isabelle Dhennin-duthille, Geneviève Spik, M. Masson, Eve Damiens, Carine Fillebeen, Joël MazurierAbstract:The main biological properties of lactoferrin are thought to concern inflammation and immunomodulation processes, including maturation of immature B and T cells. Lactoferrin accelerates T-cell maturation by inducing the expression of the CD4 surface marker. In this report, using the Jurkat T-cell line, we have shown that lactoferrin upregulates the expression of CD4 Antigen through the activation of a transduction pathway. Using an anti-phosphotyrosine antibody, lactoferrin was demonstrated to induce a cascade of phosphorylation of numerous proteins on their tyrosine residues. This tyrosine-phosphorylation was transient, reaching maxima between 5 and 10 min. We also identified the mitogen-activated protein kinase (MAP kinase) which presented an enhanced catalytic activity, reaching a maximum at 10 min of incubation with lactoferrin. Moreover, the use of inhibitors such as genistein and PD98059, tyrosine kinases and MAP kinase kinase (or MEK) inhibitors respectively, allowed us to correlate the activation of MAP kinase with the upregulation of CD4 expression. Finally, using Lck-defective Jurkat cells, our results showed that the p56(lck) (Lck) kinase is necessary for MAP kinase activity and CD4 expression. This paper demonstrates that lactoferrin activates transduction pathway(s) in lymphoblastic T-cells, and that Lck and the Erk2 isoform of MAP kinase are implicated in the upregulation of CD4, induced by lactoferrin in these cells.
-
Effect of lactoferrin on proliferation and differentiation of the Jurkat human lymphoblastic T cell line.
Archivum Immunologiae Et Therapiae Experimentalis, 1997Co-Authors: B. Y. Bi, Geneviève Spik, A.-m. Lefebvre, Joël MazurierAbstract:The effect of human lactoferrin on the human lymphoblastic T cell line (Jurkat) was tested with regard to proliferation and differentiation. Lactoferrin enhanced cell proliferation in a serum-reduced (1% fetal calf serum) culture. The stimulatory effect of lactoferrin on proliferation depended on the degree of iron saturation but the amplitude of the effect was low, similar to that obtained in the presence of serum transferrin. The proliferation stimulatory effect of lactoferrin was not observed in the presence of 10% fetal calf serum (FCS) in the culture medium. These results suggest that Fe-lactoferrin can substitute for Fe-transferrin during the prolonged culture of cells in a low serum concentration. Iron-saturated lactoferrin was also shown to promote T cell differentiation. Jurkat cells, when exposed to iron-saturated lactoferrin in the presence of 10% FCS, gradually exhibited a decrease in the cell volume, cell surface density of CD71 Antigen, the nuclear incorporation of [methyl-3H]thymidine, but an increase of the percentage of cell population in the G0/1 phase of the cell cycle. These modifications were accompanied by the appearance of CD4 Antigen at the cell surface. Therefore, in the continuous presence of lactoferrin, proliferating cells slowly enter into quiescence state, undergoing cell differentiation.
-
Immunostimulatory activity of lactotransferrin and maturation of CD4- CD8- murine thymocytes.
Immunology Letters, 1991Co-Authors: M. Zimecki, Joël Mazurier, M. Machnicki, Z. Wieczorek, J. Montreuil, Geneviève SpikAbstract:Human milk lactotransferrin at a concentration ranging from 1 to 10 micrograms/ml stimulated up to 5 times the humoral immune response to sheep red blood cells, expressed as the number of plaque-forming cells, when injected into mice 3 h before immunization. Further, lactotransferrin-treated thymocytes given intravenously into mice, enhanced the immune response to sheep red blood cells to the same extent as IL-1. In vitro, studies showed that CD4- CD8- thymocytes incubated with lactotransferrin and added to the splenocyte cultures, increased the immune response to sheep red blood cells. Flow cytometry analysis studies indicated that, after an overnight incubation with human lactotransferrin, CD4- CD8- thymocytes acquired the CD4 Antigen characteristic for the helper cell phenotype. Taken together, these results suggest that lactotransferrin stimulates the immune response by a process which involves the promotion of T cell differentiation.
Steven M Wolinsky - One of the best experts on this subject based on the ideXlab platform.
-
detection of CD4 t cells harboring human immunodeficiency virus type 1 dna by flow cytometry using simultaneous immunophenotyping and pcr driven in situ hybridization evidence of epitope masking of the CD4 cell surface molecule in vivo
Journal of Virology, 1995Co-Authors: Bruce K Patterson, Charles L Goolsby, Vida Hodara, Kenton L Lohman, Steven M WolinskyAbstract:Human immunodeficiency virus type 1 (HIV-1) infection of T cells and cells of the monocyte/macrophage lineage requires a specific interaction between the CD4 Antigen expressed on the cell surface and the HIV-1 external envelope glycoprotein (gp120). To study the association between HIV-1 infection and modulation of cell surface expression of the CD4 molecule in vivo, we examined the CD4+ T cells harboring proviral DNA obtained from HIV-1-infected individuals who had received no antiretroviral therapy for at least 90 days. Simultaneous immunophenotyping of CD4 cell surface expression and PCR-driven in situ hybridization for HIV-1 DNA were used to resolve the CD4+ T cells into distinct populations predicted upon the presence or absence of proviral DNA. Among the HIV-1-infected study subjects, the percentage of CD4+ T cells harboring proviral DNA ranged from 17.3 to 55.5%, with a mean of 40.5%. Cell surface fluorescent staining with anti-CD4 antibody directed against a non-gp120 binding site-related epitope (L120) or a conformation-dependent epitope of the gp120 binding site (Leu 3A) demonstrated either an equivalent or a 1.5- to 3-fold-lower cell surface staining intensity for the HIV-1 DNA-positive subpopulation relative to the HIV-1 DNA-negative subpopulation, respectively. These data suggest that masking or alteration of specific epitopes on the CD4 molecule occurs after viral infection.
Edward J. Wawrzynczak - One of the best experts on this subject based on the ideXlab platform.
-
Blocked and non-blocked ricin immunotoxins against the CD4 Antigen exhibit higher cytotoxic potency than a ricin A chain immunotoxin potentiated with ricin B chain or with a ricin B chain immunotoxin
Cancer Immunology Immunotherapy, 1991Co-Authors: Edward J. Wawrzynczak, Graham J. Watson, Alan J. Cumber, Raymond V. Henry, Geoffrey D. Parnell, E. Peter Rieber, Philip E. ThorpeAbstract:An immunotoxin consisting of ricin A chain linked to the monoclonal antibody M-T151, recognising the CD4 Antigen, was weakly toxic to the human T-lymphoblastoid cell line CEM in tissue culture. The incorporation of [^3H]leucine by CEM cells was inhibited by 50% at an M-T151-ricin-A-chain concentration (IC_50) of 4.6 nM compared with an IC_50 of 1.0 pM for ricin. In contrast, immunotoxins made by linking intact ricin to M-T151 in such a way that the galactose-binding sites of the B chain subunit were either blocked sterically by the antibody component or were left unblocked, were both powerfully cytotoxic with IC_50 values of 20–30 pM. The addition of ricin B chain to CEM cells treated with M-T151—ricin-A-chain enhanced cytotoxicity by only eight-fold indicating that isolated B chain potentiated the action of the A chain less effectively than it did as an integral component of an intact ricin immunotoxin. Ricin B chain linked to goat anti-(mouse immunoglobulin) also potentiated weakly. Lactose completely inhibited the ability of isolated ricin B chain to potentiate the cytotoxicity of M-T151—ricin-A-chain and partially (3- to 4-fold) inhibited the cytotoxicity of the blocked and non-blocked ricin immunotoxins. Thus, in this system, the galactose-binding sites of the B chain contributed to cell killing regardless of whether isolated B chain was associated with the A chain immunotoxin or was present in blocked or non-blocked form as part of an intact ricin immunotoxin. The findings suggest that the blocked ricin immunotoxin may become unblocked after binding to the target Antigen to re-expose the cryptic galactose-binding sites. However, the unblocking cannot be complete because the maximal inhibition of [^3H]leucine incorporation by the blocked immunotoxin was only 80% compared with greater than 99% inhibition by the non-blocked immunotoxin.
-
Blocked and non-blocked ricin immunotoxins against the CD4 Antigen exhibit higher cytotoxic potency than a ricin A chain immunotoxin potentiated with ricin B chain or with a ricin B chain immunotoxin.
Cancer Immunology Immunotherapy, 1991Co-Authors: Edward J. Wawrzynczak, Graham J. Watson, Alan J. Cumber, Raymond V. Henry, Geoffrey D. Parnell, E. Peter Rieber, Philip E. ThorpeAbstract:An immunotoxin consisting of ricin A chain linked to the monoclonal antibody M-T151, recognising the CD4 Antigen, was weakly toxic to the human T-lymphoblastoid cell line CEM in tissue culture. The incorporation of [3H]leucine by CEM cells was inhibited by 50% at an M-T151-ricin-A-chain concentration (IC50) of 4.6 nM compared with an IC50 of 1.0 pM for ricin. In contrast, immunotoxins made by linking intact ricin to M-T151 in such a way that the galactose-binding sites of the B chain subunit were either blocked sterically by the antibody component or were left unblocked, were both powerfully cytotoxic with IC50 values of 20–30 pM. The addition of ricin B chain to CEM cells treated with M-T151—ricin-A-chain enhanced cytotoxicity by only eight-fold indicating that isolated B chain potentiated the action of the A chain less effectively than it did as an integral component of an intact ricin immunotoxin. Ricin B chain linked to goat anti-(mouse immunoglobulin) also potentiated weakly.
Saburo Murakami - One of the best experts on this subject based on the ideXlab platform.
-
thyroid involvement by malignant histiocytosis of langerhans cell type
Clinical Endocrinology, 1996Co-Authors: Shinji Kitahama, Makoto Iitaka, Tadashi Shimizu, Naoki Serizawa, Nobuhiko Fukasawa, Shiro Miura, Satomi Kawasaki, Kayo Yamanaka, Yoshito Kawakami, Saburo MurakamiAbstract:Involvement of the thyroid gland by Langerhans' cell histiocytosis is quite rare. We describe the case of a 58-year-old man referred for treatment of a progressively enlarging goitre. The trachea was severely stenotic and adjacent structures such as the left carotid vein and the thyroid cartilage were also involved. Central diabetes insipidus and severe combined immunodeficiency were associated. Although fine needle aspiration biopsy of the thyroid was initially interpreted as papillary carcinoma, anaplastic thyroid cancer was suspected. Treatment with prednisolone, doxorubicin and irradiation controlled the tracheal compression. A diagnosis of thyroid Langerhans' cell histiocytosis was finally made on the basis of the presence of Birbeck granules and CD1a and CD4 Antigen in the thyroid tumour cells. Furthermore, positive staining for CD68 and lysozyme suggested that the tumour cells may have had the character of phagocytic cells in addition to their dendritic cell nature. This is the first case of thyroid involvement by malignant histicytosis of Langerhans' cell type with unusual phagocytic markers.