Glucocorticoid-Induced Tumor Necrosis Factor Receptor Family-Related Protein Triggering Enhances HIV-Specific CD4 super(+) T Cell Cytokine Secretion and protects HIV-Specific CD4 super(+) T Cells from Apoptosis

• Published in: The Journal of infectious diseases Vol. 196; no. 1; pp. 43 - 49
• Main Authors: Lahey, T P, Loisel, S D, Wieland-Alter, W
• Format: Journal Article
• Language: English
• Published: 01.07.2007
• Subjects: Human immunodeficiency virus
• ISSN: 0022-1899

Human immunodeficiency virus (HIV)-specific CD4 super(+) T cell cytokine secretion is characteristically weak during HIV infection, in part because HlV-specific CD4 super(+) T cells undergo massive apoptotic deletion. Glucocorticoid-induced tumor necrosis factor (TNF) receptor family-related (GITR) protein triggering enhances murine antigen-specific T cell cytokine secretion by protecting T cells from apoptosis. Therefore, we investigated the impact of GITR triggering on HIV-specific CD4 super(+) T cell cytokine secretion and on apoptosis of HlV-specific CD4 super(+) T cells. In HIV-infected subjects, CD4 super(+) T cell surface expression of GITR was greater than that in uninfected control subjects, and phytohemagglutinin induction of additional GITR expression was impaired. However, antibody triggering of GITR significantly increased HIV-specific CD4 super(+) T cell expression of TNF- alpha and interferon (IFN)- gamma . The percentage increase in HIV-specific CD4 super(+) T cell expression of TNF- alpha correlated directly with the absolute peripheral CD4 super(+) T cell count. Furthermore, GITR triggering reduced the expression of intracellular activated caspase-3 in HIV-specific CD4 super(+) T cells. Taken together, these data suggest that, despite abnormal GITR expression during HIV infection, GITR triggering enhances HIV-specific CD4 super(+) T cell cytokine expression and protects HIV-specific CD4 super(+) T cells from apoptosis.