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Reena Rajasuriar - One of the best experts on this subject based on the ideXlab platform.
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CD4 t cell deficiency in hiv patients responding to antiretroviral therapy is associated with increased expression of interferon stimulated genes in CD4 t cells
The Journal of Infectious Diseases, 2011Co-Authors: Sonia Fernandez, Sara Tanaskovic, Karla J Helbig, Reena Rajasuriar, Marit Kramski, John M Murray, Michael R Beard, Damian F J Purcell, Sharon R Lewin, P B PriceAbstract:Most patients with human immunodeficiency virus (HIV) who remain CD4(+) T-cell deficient on antiretroviral therapy (ART) exhibit marked immune activation. As CD4(+) T-cell activation may be mediated by microbial translocation or interferon-alpha (IFN-α), we examined these factors in HIV patients with good or poor CD4(+) T-cell recovery on long-term ART. Messenger RNA levels for 3 interferon-stimulated genes were increased in CD4(+) T cells of patients with poor CD4(+) T-cell recovery, whereas levels in patients with good recovery did not differ from those in healthy controls. Poor CD4(+) T-cell recovery was also associated with CD4(+) T-cell expression of markers of activation, senescence, and apoptosis, and with increased serum levels of the lipopolysaccharide receptor and soluble CD14, but these were not significantly correlated with expression of the interferon-stimulated genes. Therefore, CD4(+) T-cell recovery may be adversely affected by the effects of IFN-α, which may be amenable to therapeutic intervention.
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biological determinants of immune reconstitution in hiv infected patients receiving antiretroviral therapy the role of interleukin 7 and interleukin 7 receptor α and microbial translocation
The Journal of Infectious Diseases, 2010Co-Authors: Reena Rajasuriar, David R Booth, Ajantha Solomon, Kyra Chua, Tim Spelman, Maelenn Gouillou, Timothy E Schlub, Miles P Davenport, Suzanne M CroweAbstract:Background. Multiple host factors may influence CD4(+) T cell reconstitution in human immunodeficiency virus (HIV)-infected patients after suppressive antiretroviral therapy (ART). We hypothesized that residual immune activation and polymorphisms in the interleukin 7 (IL-7) receptor alpha (IL-7R alpha) gene were important for immune recovery. Methods. We examined HIV-infected patients receiving suppressive ART (n = 96) for their IL-7R alpha haplotypes and measured levels of lipopolysaccharide (LPS), soluble CD14, and IL-7 in plasma samples collected before and after ART initiation. Levels of soluble IL-7R alpha were measured in HIV-infected patients with IL-7R alpha haplotype 2 (n = 11) and those without IL-7R alpha haplotype 2 (n = 22). Multivariate analysis was used to identify variables associated with faster recovery to CD4(+) T cell counts of > 500 and > 200 cells/mu L. Results. Both LPS and soluble CD14 levels were significantly decreased with ART (P 500 cells/mu L was significantly associated with higher baseline CD4(+) T cell count, younger age, lower pre-ART LPS level, higher pre-ART soluble CD14 level, lower pre-ART IL-7 level, and IL-7R alpha haplotype 2 (hazard ratio, 1.50; 95% confidence interval, 1.03-2.19; P = .034). HIV-infected patients with haplotype 2 had significantly lower soluble IL-7R alpha levels compared with those of patients without haplotype 2 (P 500 cells/mu L.
A.h. Penninks - One of the best experts on this subject based on the ideXlab platform.
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Recovery from chemically induced thymus atrophy starts with CD4- CD8- CD2high TcR alpha beta-/low thymocytes and results in an increased formation of CD4- CD8- TcR alpha beta high thymocytes.
Immunology, 1993Co-Authors: Raymond Pieters, B. W. Lam, Marianne Bol, Willem Seinen, Nanne Bloksma, A.h. PenninksAbstract:Regeneration of the thymus was studied in rats that were treated with a single oral dose of the organotin compound di-n-butyltin dichloride (DBTC). After an initial maximum depletion of cortical BrdU+ thymocytes on day 2 after treatment, repopulation appeared to start on day 3 as indicated by an increased number of BrdU+ cells in the subcapsular region. On day 5, when thymocyte depletion was most pronounced, a relative increase of BrdU+ cells was observed all over the cortex. In comparison with controls, the thymoblast population on day 5 appeared to harbour increased numbers of CD4- CD8- and immature CD4- CD8+ CD53- thymoblasts, while the number of CD4+ CD8+ blasts had decreased. In comparison with day 3, however, the number of CD4+ CD8+ blasts had increased again. Results together have been interpreted as indicative for thymus regeneration starting from CD4- CD8- blasts which differentiate to immature CD4- CD8+ and then to CD4+ CD8+ blasts. Further characterization revealed that the majority of the CD4- CD8- and CD4- CD8+ CD53- blasts expressed high levels of CD2 and no or low levels of T-cell receptor (TcR) alpha beta. The high expression of CD2 on repopulating thymoblasts may be an additional indication of their activated state and for a role of interaction with the ligand LFA-3 on thymic epithelial cells during this phase of thymocyte differentiation. The number of CD4- CD8- TcR alpha beta high cells was increased on day 5 after dosing. The origin of this population and the possible implication of its development during thymus regeneration after chemically induced thymus atrophy are discussed.
M Fotino - One of the best experts on this subject based on the ideXlab platform.
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the molecular basis for the synergism between the cd3 alpha beta t cell receptor and the cd2 antigen derived signals in promoting t cell proliferation
Transplantation, 1991Co-Authors: P. K. Sehajpal, Bernd Zanker, V.k. Murthi, A. Subramaniam, V. K. Sharma, D. Estin, E. Y. Skonik, Kenneth J. Wieder, Gerd Walz, M FotinoAbstract:Northern blot analysis and a highly sensitive methodology for mRNA phenotyping, polymerase chain reaction (PCR), were used to explore the basis for the synergism between CD3/alpha beta T cell receptor (TCR) and the CD2 antigen-derived signals in promoting proliferation of T cells. Northern blotting of RNA isolated from highly purified normal human T cells revealed that crosslinking of anti-TCR-1 (a mAb directed at a framework determinant of the TCR) and OKT11 (a mAb directed at the SRBC-binding epitope of the CD2 antigen) induced the expression of the interleukin-2 gene and the gene for IL-2 receptor alpha, mRNA phenotyping by PCR revealed that crosslinkage of TCR with the CD2 antigen, and not independent crosslinking of TCR or the CD2 antigen, results in the induction of IL-2, IL-2 receptors alpha and beta, and IL-4-specific transcripts. Highly purified CD4+ T cells, as well as CD8+ T cells proliferated by crosslinking TCR with CD2 antigen. Moreover, crosslinkage of TCR with the CD2 antigen and not of either antigen with the CD4 antigen (on the surface of CD4+ T cells) or the CD8 antigen (on the surface of CD8+ T cells) resulted in marked proliferation. Our demonstration that the CD2 antigen-derived signal(s) contribute to the expression of growth promoting genes elicited via the TCR, and that the CD2 antigen is more efficient compared with the CD4 or CD8 antigen in evoking T cell proliferation, suggests that autoimmunity as well as alloimmunity might be regulated by targeting the CD2 antigen.
A N Barclay - One of the best experts on this subject based on the ideXlab platform.
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a sensitive assay for detecting low affinity interactions at the cell surface reveals no additional ligands for the adhesion pair rat cd2 and CD48
European Journal of Immunology, 1995Co-Authors: Marion H. Brown, S Preston, A N BarclayAbstract:The ligand for the T cell antigen CD2 is CD48 in rodents, but CD58 in humans. The extracellular parts of these three antigens are structurally related in that all contain two immunoglobulin superfamily (IgSF) domains. There have been reports of alternative ligands for CD2 in the human, but not so far in rodents. We describe the analysis of ligands for rat CD2 and CD48 using fluorescent beads capable of displaying a high ligand density and detecting low-affinity interactions like that of CD2 with CD48 (Kd = 60-90 microM). Monovalent chimeric proteins containing the two IgSF domains of rat CD48 or CD2 and domains 3 and 4 of rat CD4 (CD4d3+4) were anchored to fluorescent covaspheres via a CD4 monoclonal antibody (mAb) with the CD48 or CD2 domains available for ligand binding. Multivalent CD48-CD4d3+4 covaspheres gave strong specific binding to rat CD2 expressed on the surface of transfected Jurkat cells. CD48-CD4d3+4 was compared with CD48-IgG and CD48-IgM as tools for detecting binding at the cell surface. Soluble divalent CD48-IgG and decavalent CD48-IgM bound to soluble CD2 with a Koff of around 10(-3) s-1 as determined using a BIAcore biosensor. However, binding to cells by CD48-IgG and CD48-IgM was only detectable when they were immobilized on covaspheres and represented no increase in sensitivity over CD48-CD4 covaspheres when tested for binding to cells expressing high and low levels of CD2. CD48-CD4d3+4 covaspheres only bound to rat cells expressing CD2. In the reverse orientation, bindign of CD2-CD4d3+4 covaspheres was dependent on expression of CD48. Pre-incubation of cells with CD2 or CD48 mAb abolished all binding of CD48-CD4d3+4 or CD2-CD4d3+4, respectively. The data provide no evidence for an alternative ligand for rat CD2 or CD48.
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The NH2-terminal domain of rat CD2 binds rat CD48 with a low affinity and binding does not require glycosylation of CD2.
European journal of immunology, 1993Co-Authors: P A Van Der Merwe, A N Barclay, D C Mcpherson, Marion H. Brown, Jason G. Cyster, Alan F. Williams, Simon J. DavisAbstract:CD2, CD48 and CD58 are structurally similar cell adhesion-molecules forming a subset of the immunoglobulin superfamily (IgSF). In humans CD58 is a ligand for CD2 while in mice CD2 binds CD48. We constructed a soluble chimeric molecule comprising the extracellular portion of rat CD48 and domains 3 and 4 of rat CD4 (sCD48-CD4) and used it to examine whether CD2 is a ligand for CD48 in rats. sCD48-CD4-coated polystyrene Dynabeads formed rosettes on rat CD2-transfected COS-7 cells, and this rosetting was blocked by anti-CD2 (OX34) and anti-CD48 (OX45) monoclonal antibodies. We used sucrose-gradient ultracentrifugation to show that sCD48-CD4 binds, in solution, to soluble forms of rat CD2 including the single NH2-terminal IgSF domain of rat CD2 expressed in bacteria. The upper limit of the affinity of the rat CD48-CD2 interaction is 4 x 10(5) M-1, lower than the published affinity of human CD2 for CD58. These results show that rat CD48 binds CD2 on its NH2-terminal IgSF domain with a low affinity and that binding is independent of glycosylation.
Raymond Pieters - One of the best experts on this subject based on the ideXlab platform.
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Recovery from chemically induced thymus atrophy starts with CD4- CD8- CD2high TcR alpha beta-/low thymocytes and results in an increased formation of CD4- CD8- TcR alpha beta high thymocytes.
Immunology, 1993Co-Authors: Raymond Pieters, B. W. Lam, Marianne Bol, Willem Seinen, Nanne Bloksma, A.h. PenninksAbstract:Regeneration of the thymus was studied in rats that were treated with a single oral dose of the organotin compound di-n-butyltin dichloride (DBTC). After an initial maximum depletion of cortical BrdU+ thymocytes on day 2 after treatment, repopulation appeared to start on day 3 as indicated by an increased number of BrdU+ cells in the subcapsular region. On day 5, when thymocyte depletion was most pronounced, a relative increase of BrdU+ cells was observed all over the cortex. In comparison with controls, the thymoblast population on day 5 appeared to harbour increased numbers of CD4- CD8- and immature CD4- CD8+ CD53- thymoblasts, while the number of CD4+ CD8+ blasts had decreased. In comparison with day 3, however, the number of CD4+ CD8+ blasts had increased again. Results together have been interpreted as indicative for thymus regeneration starting from CD4- CD8- blasts which differentiate to immature CD4- CD8+ and then to CD4+ CD8+ blasts. Further characterization revealed that the majority of the CD4- CD8- and CD4- CD8+ CD53- blasts expressed high levels of CD2 and no or low levels of T-cell receptor (TcR) alpha beta. The high expression of CD2 on repopulating thymoblasts may be an additional indication of their activated state and for a role of interaction with the ligand LFA-3 on thymic epithelial cells during this phase of thymocyte differentiation. The number of CD4- CD8- TcR alpha beta high cells was increased on day 5 after dosing. The origin of this population and the possible implication of its development during thymus regeneration after chemically induced thymus atrophy are discussed.