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The most widely accepted theory for the massive §depletion of CD4+ T cells in HIV-1 infection §involves depletion of non-infected cells through §immune activation. A specialized cell population, §the T regulatory cells (Tregs), exists to help limit §chronic inflammation by suppressing the immune §activation induced by infectious diseases. We used §an SIV/pigtailed macaque model of HIV-1 disease to §elucidate the role of Tregs in HIV-1-induced §depletion of CD4+ T cells in lymphoid tissue during §the acute phase of infection. From this model, we §learned that Tregs play a significant role in §controlling the apoptotic loss of CD4+ T cells §resulting from high levels of generalized immune §activation. Using assays developed in the macaque §model, we next studied the role of Tregs in elite §suppressors who are HIV-1-infected individuals that §maintain normal CD4+ T cell counts and control §viremia without therapy. The assays developed §in our laboratory should be especially useful to §the future studies of both virologists and §immunologists.