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A Low T Regulatory Cell Response May Contribute to Both Viral Control and Generalized Immune Activation in HIV Controllers 1 2 1 2 1 Peter W. Hunt *, Alan L. Landay , Elizabeth Sinclair , Jeffrey A. Martinson , Hiroyu Hatano , Brinda 1 1,3 1,3 1 2 1 Emu , Philip J. Norris , Michael P. Busch , Jeffrey N. Martin , Cicely Brooks , Joseph M. McCune , Steven G. Deeks1 1 Departments of Medicine and Laboratory Medicine, University of California San Francisco, San Francisco, California, United States of America, 2 Department of Immunology/Microbiology, Rush University Medical Center, Chicago, Illinois, United States of America, 3 Blood Systems Research Institute, San Francisco, California, United States of America Abstract HIV-infected individuals maintaining undetectable viremia in the absence of therapy (HIV controllers) often maintain high HIV-specific T cell responses, which has spurred the development of vaccines eliciting HIV-specific T cell responses. However, controllers also often have abnormally high T cell activation levels, potentially contributing to T cell dysfunction, CD4+ T cell depletion, and non-AIDS morbidity. We hypothesized that a weak T regulatory cell (Treg) response might contribute to the control of viral replication in HIV controllers, but might also contribute to generalized immune activation, contributing to CD4+ T cell loss. To address these hypotheses, we measured frequencies of activated (CD38+ HLA-DR+), regulatory (CD4+CD25+CD127dim), HIV-specific, and CMV-specific T cells among HIV controll