Journal
CLINICAL IMMUNOLOGY
Volume 132, Issue 2, Pages 234-245Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.clim.2009.03.531
Keywords
4-1BB expression; OX40 expression; HIV-specific CD4+T cells; CMV-specific CD4+T cells
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Funding
- Colorado Center for AIDS Research (CFAR) Pilot Project
- NIH [A1076161]
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CD4+ T cell dysfunction in subjects with chronic HIV infection is in part due to an imbalance of costimulatory and coinhibitory receptors. We report that virus-specific CD4+ T cells expressing 4-1BB (CD137) or OX40 (CD134) produced more IL-2 than cells lacking these costimulatory receptors (P<0.05) and that 4-1BB was expressed at a tower level on HIV- than CMV-specific IFN-gamma and IL-2 producing CD4+ T cells (P<0.0001 and P<0.01, respectively). Suppression of viral replication with antiretroviral therapy was associated with increased 4-1BB expression on HIV- and CMV-specific IL-2 producing CD4+ T cells (P<0.05 and P<0.01, respectively) and the percentage of IL-2 producing HIV-specific CD4+ T cells that expressed 411313 was inversely correlated with HIV plasma viral load (r=-0.75, P=0.007). These findings indicate that the loss of 4-1BB on HIV-specific CD4+ T cells is associated with viral replication and that it may contribute to reduced IL-2 production observed during chronic infection. (C) 2009 Elsevier Inc. All rights reserved.
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