In Vivo CD8+ T-Cell Suppression of SIV Viremia Is Not Mediated by CTL Clearance of Productively Infected Cells

PLoS Pathogens

Caroline C. Ignacio¹  Sumathi Sankaran-Walters¹  Joseph K. Wong²  David J. Looney²  Satish K. Pillai³  Rodin Porrata³  Satya Dandekar³  Theresa Russell³  Matthew C. Strain³  Elizabeth Reay⁴ 

[1] Department of Medical Microbiology and Immunology, University of California Davis, Davis, California, United States of America;Department of Medicine, University of California San Francisco, San Francisco, California, United States of America;Department of Medicine, VA San Diego Healthcare System, University of California San Diego, La Jolla, California, United States of America;Department of Physics, University of California Berkeley, Berkeley, California, United States of America

关键词: Cytotoxic T cells;    T cells;    SIV;    Viral load;    Macaque;    Blood plasma;    Antibodies;    HIV;   

DOI  :  10.1371/journal.ppat.1000748

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

The CD8+ T-cell is a key mediator of antiviral immunity, potentially contributing to control of pathogenic lentiviral infection through both innate and adaptive mechanisms. We studied viral dynamics during antiretroviral treatment of simian immunodeficiency virus (SIV) infected rhesus macaques following CD8+ T-cell depletion to test the importance of adaptive cytotoxic effects in clearance of cells productively infected with SIV. As previously described, plasma viral load (VL) increased following CD8+ T-cell depletion and was proportional to the magnitude of CD8+ T-cell depletion in the GALT, confirming a direct relationship between CD8+ T-cell loss and viral replication. Surprisingly, first phase plasma virus decay following administration of antiretroviral drugs was not slower in CD8+ T-cell depleted animals compared with controls indicating that the short lifespan of the average productively infected cell is not a reflection of cytotoxic T-lymphocyte (CTL) killing. Our findings support a dominant role for non-cytotoxic effects of CD8+ T-cells on control of pathogenic lentiviral infection and suggest that cytotoxic effects, if present, are limited to early, pre-productive stages of the viral life cycle. These observations have important implications for future strategies to augment immune control of HIV.

【 授权许可】

CC BY