Preferential Apoptosis of HIV-1-Specific CD4+ T Cells

• Published in: The Journal of immunology (1950) Vol. 174; no. 4; pp. 2196 - 2204
• Main Authors: Yue, Feng Yun, Kovacs, Colin M, Dimayuga, Rowena C, Gu, Xiao Xiao Jenny, Parks, Paul, Kaul, Rupert, Ostrowski, Mario A
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.02.2005
• Subjects: Adult; Apoptosis - immunology; CASP8 and FADD-Like Apoptosis Regulating Protein; Caspase 3; Caspase 8; Caspase 9; Caspase Inhibitors; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD4-Positive T-Lymphocytes - pathology; CD4-Positive T-Lymphocytes - virology; Cytomegalovirus - immunology; Disease Progression; Disease Susceptibility - immunology; Epitopes, T-Lymphocyte - immunology; fas Receptor - immunology; Female; Free Radicals - antagonists & inhibitors; HIV Infections - immunology; HIV Infections - pathology; HIV-1 - immunology; Humans; Immune Sera - pharmacology; Immunologic Memory; Interferon-gamma - biosynthesis; Intracellular Signaling Peptides and Proteins - metabolism; Intracellular Signaling Peptides and Proteins - physiology; Proto-Oncogene Proteins c-bcl-2 - biosynthesis; Proto-Oncogene Proteins c-bcl-2 - physiology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.174.4.2196

In contrast to other viral infections such as CMV, circulating frequencies of HIV-1-specific CD4+ T cells in peripheral blood are quantitatively diminished in the majority of HIV-1-infected individuals. One mechanism for this quantitative defect is preferential infection of HIV-1-specific CD4+ T cells, although <10% of HIV-1-specific CD4+ T cells are infected. Apoptosis has been proposed as an important contributor to the pathogenesis of CD4+ T cell depletion in HIV/AIDS. We show here that, within HIV-1-infected individuals, a greater proportion of ex vivo HIV-1-specific CD4+ T cells undergo apoptosis compared with CMV-specific CD4+ T cells (45 vs 7.4%, respectively, p < 0.05, in chronic progressors). The degree of apoptosis within HIV-1-specific CD4+ T cells correlates with viral load and disease progression, and highly active antiretroviral therapy abrogates these differences. The data support a mechanism for apoptosis in these cells similar to that found in activation-induced apoptosis through the TCR, resulting in oxygen-free radical production, mitochondrial damage, and caspase-9 activation. That HIV-1 proteins can also directly enhance activation-induced apoptosis supports a mechanism for a preferential induction of apoptosis of HIV-1-specific CD4+ T cells, which contributes to a loss of immunological control of HIV-1 replication.