T memory stem cells and HIV: a long-term relationship

Abstract

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" (TSCM), 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+ TSCM cells represent a core element of the HIV-1 reservoir in patients treated with suppressive antiretroviral therapy (ART) and that relative resistance of CD4+ TSCM cells to SIV represents a distinguishing feature of non-pathogenic SIV infection in natural hosts. This article summarizes recent studies investigating the role of TSCM in HIV/SIV infection.

Figure 1

Schematic of CD4+ memory T cell homeostasis (A) and proposed relative contribution of CD4+ memory subsets to the persistent reservoir of HIV/SIV (B, top panel). In (B) the potential effects of drugs promoting enhanced self-renewal (middle panel) or enhanced differentiation (bottom panel) of T_SCM on the overall CD4+ memory T cell reservoir are shown. Stars represent cells latently infected with HIV/SIV.