T Memory Stem Cells and HIV: a Long-Term Relationship

In analogy to many tissues in which mature, terminally differentiated cells are continuously replenished by the progeny of less differentiated, long-lasting stem cells, it has been suspected that memory T lymphocytes might contain small numbers of stem cell-like cells. However, only recently have such cells been physically identified and isolated from humans, mice, and nonhuman primates. These cells, termed "T memory stem cells" (T-SCM), represent approximately 2-4% of all circulating T lymphocytes, seem to be extremely durable, and can rapidly differentiate into more mature central memory, effector memory, and effector T cells, while maintaining their own pool size through homeostatic self-renewal. Although it is becoming increasingly evident that that these cells have critical roles for T cell homeostasis and maintaining life-long cellular immunity against microbial pathogens during physiological conditions, they also seem intrinsically involved in many key aspects of HIV/SIV disease pathogenesis. Current data suggest that CD4+T-SCM cells represent a core element of the HIV-1 reservoir in patients treated with suppressive antiretroviral therapy (ART) and that relative resistance of CD4+ T-SCM cells to SIV represents a distinguishing feature of non-pathogenic SIV infection in natural hosts. This article summarizes recent studies investigating the role of T-SCM in HIV/SIV infection.