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JAIDS Journal of Acquired Immune Deficiency Syndromes:
doi: 10.1097/QAI.0b013e3182a1bc81
Basic and Translational Science

Susceptibility to CD8 T-Cell–Mediated Killing Influences the Reservoir of Latently HIV-1–Infected CD4 T Cells

Buzon, Maria J. PhD*,†; Yang, Yue MD*,†; Ouyang, Zhengyu PhD; Sun, Hong MD†,‡; Seiss, Katherine BSc; Rogich, Jerome BSc; Le Gall, Sylvie PhD; Pereyra, Florencia MD†,§; Rosenberg, Eric S. MD*; Yu, Xu G. MD; Lichterfeld, Mathias MD, PhD*

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Abstract

Background: HIV-1 establishes a lifelong infection in the human body, but host factors that influence viral persistence remain poorly understood. Cell-intrinsic characteristics of CD4 T cells, the main target cells for HIV-1, may affect the composition of the latent viral reservoir by altering the susceptibility to CD8 T-cell–mediated killing.

Results: We observed that susceptibilities of CD4 T cells to CD8 T-cell–mediated killing, as determined in direct ex vivo assays, were significantly higher in persons with natural control of HIV-1 (elite controllers) than in individuals effectively treated with antiretroviral therapy. These differences were most pronounced in naive and in terminally differentiated CD4 T cells and corresponded to a reduced viral reservoir size in elite controllers. Interestingly, the highest susceptibility to CD8 T-cell–mediated killing and lowest reservoirs of cell-associated HIV-1 DNA was consistently observed in elite controllers expressing the protective HLA class I allele B57.

Conclusions: These data suggest that the functional responsiveness of host CD4 T cells to cytotoxic effects of HIV-1–specific CD8 T cells can contribute to shaping the structure and composition of the latently infected CD4 T-cell pool.

© 2014 by Lippincott Williams & Wilkins

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