Gut Mucosal FOXP3 Regulatory CD4 T Cells and Nonregulatory

The gastrointestinal tract represents a major site for human and simian immunodeficiency virus (HIV and SIV) replication and CD4 T-cell depletion. Despite severe depletion of mucosal CD4 T cells, FOXP3 regulatory CD4 T cells (Treg) are highly increased in the gut mucosa of chronically HIV-infected individuals and may contribute to HIV pathogenesis, either by their immunosuppressive function or as a significant target cell population for virus production. Little is known about the susceptibility of mucosal Treg to viral infection and the longitudinal effect of HIV/SIV infection on Treg dynamics. In this study, we determined the level of SIV infection in Treg and nonregulatory CD4 T cells (non-Treg) isolated from the colon of SIV-infected rhesus macaques. The dynamics of mucosal Treg and alterations in the mucosal CD4 T-cell pool were examined longitudinally. Our findings indicate that mucosal Treg were less susceptible to productive SIV infection than non-Treg and thus were selectively spared from SIV-mediated cell death. In addition to improved survival, local expansion of Treg by SIV-induced proliferation of the mucosal CD4 T-cell pool facilitated the accumulation of mucosal Treg during the course of infection. High frequency of mucosal Treg in chronic SIV infection wa