Chemokine and cytokine mediated loss of regulatory T cells in lymph nodes during pathogenic simian immunodeficiency virus infection

Regulatory T cells (T-reg) play key roles in immune regulation through multiple modes of suppression. The effects of HIV-1 infection on T-reg levels in lymphoid tissues remain incompletely understood. To explore this issue, we have measured the levels of forkhead box protein 3 (FOXP3)-positive cells and associated immunomodulatory genes in a pathogenic simian immunodeficiency virus/macaque model and found that a loss of T-reg in lymph nodes occurred following simian immunodeficiency virus infection. Changes in expression of the ligands for CXCR3, CCR4, and CCR7 and the cytokines TGF-beta and IL-2 were all linked to this loss of T-reg, which in turn was linked with increased levels of cellular activation. Our findings identify three mechanisms that likely contribute to SIV-driven loss of T-reg, including reduced levels of cytokines associated with T-reg differentiation and altered expression of agonist and antagonist chemokines. The loss of T-reg and the associated cellular activation in lymphoid tissues is consistent with the events in HIV-1-infected individuals and suggest that components of the T-reg differentiation and trafficking network could be targets for therapeutic intervention.