Divergent CD4+ T Memory Stem Cell Dynamics in Pathogenic and Nonpathogenic Simian Immunodeficiency Virus Infections

Recent studies have identified a subset of memory T cells with stem cell-like properties (T SCM ) that include increased longevity and proliferative potential. In this study, we examined the dynamics of CD4 + T SCM during pathogenic SIV infection of rhesus macaques (RM) and nonpathogenic SIV infection of sooty mangabeys (SM). Whereas SIV-infected RM show selective numeric preservation of CD4 + T SCM , SIV infection induced a complex perturbation of these cells defined by depletion of CD4 + CCR5 + T SCM , increased rates of CD4 + T SCM proliferation, and high levels of direct virus infection. The increased rates of CD4 + T SCM proliferation in SIV-infected RM correlated inversely with the levels of central memory CD4 + T cells. In contrast, nonpathogenic SIV infection of SM evidenced preservation of both CD4 + T SCM and CD4 + central memory T cells, with normal levels of CD4 + T SCM proliferation, and lack of selective depletion of CD4 + CCR5 + T SCM . Importantly, SIV DNA was below the detectable limit in CD4 + T SCM from 8 of 10 SIV-infected SM. We propose that increased proliferation and infection of CD4 + T SCM may contribute to the pathogenesis of SIV infection in RM.