Differential impact of in vivo CD8⁺ T lymphocyte depletion in controller versus progressor simian immunodeficiency virus-infected macaques

Numerous studies have demonstrated that CD8⁺ T lymphocytes suppress virus replication during human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) infection. However, the mechanisms underlying this activity of T cells remain incompletely understood. Here, we conducted CD8⁺ T lymphocyte depletion in 15 rhesus macaques (RMs) infected intravenously (i.v.) with SIV_mac239. At day 70 postinfection, the animals (10 progressors with high viremia and 5 controllers with low viremia) were CD8 depleted by i.v. administration of the antibody M-T807R1. As expected, CD8 depletion resulted in increased virus replication, more prominently in controllers than progressors, which correlated inversely with predepletion viremia. Of note, the feature of CD8⁺ T lymphocyte predepletion that correlated best with the increase in viremia postdepletion was the level of CD8⁺ T-bet⁺ lymphocytes. We next found that CD8 depletion resulted in a homogenous increase of SIV RNA in superficial and mesenteric lymph nodes, spleen, and the gastrointestinal tract of both controllers and progressors. Interestingly, the level of SIV DNA increased postdepletion in both CD4⁺ central memory T lymphocytes (T_CM) and CD4⁺ effector memory T lymphocytes (T_EM) in progressor RMs but decreased in the CD4⁺ T_CM of 4 out of 5 controllers. Finally, we found that CD8 depletion is associated with a greater increase in CD4⁺ T lymphocyte activation (measured by Ki-67 expression) in controllers than in progressors. Overall, these data reveal a differential impact of CD8⁺ T lymphocyte depletion between controller and progressor SIV-infected RMs, emphasizing the complexity of the in vivo antiviral role of CD8⁺ T lymphocytes.