Superior T memory stem cell persistence supports long-lived T cell memory

TLDR

Long‑lived memory T cells persist without antigen, yet their maintenance mechanisms are unclear; a self‑renewing, multipotent subset called TSCM may serve as a lifelong reservoir, but its in vivo dynamics remain undefined due to limited animal models. Vaccination strategies designed to elicit durable cellular immunity should target the generation of TSCM cells. We identified T cells with a TSCM phenotype and stem cell–like properties in nonhuman primates. TSCM cells are the least‑differentiated memory subset, functionally distinct from conventional memory cells, act as precursors of central memory, localize preferentially to lymph nodes, are generated during acute viral infection, preferentially survive antigen elimination, and stably persist long term, providing a mechanism for long‑term T cell memory.

Abstract

Long-lived memory T cells are able to persist in the host in the absence of antigen; however, the mechanism by which they are maintained is not well understood. Recently, a subset of human T cells, stem cell memory T cells (TSCM cells), was shown to be self-renewing and multipotent, thereby providing a potential reservoir for T cell memory throughout life. However, their in vivo dynamics and homeostasis still remain to be defined due to the lack of suitable animal models. We identified T cells with a TSCM phenotype and stem cell–like properties in nonhuman primates. These cells were the least-differentiated memory subset, were functionally distinct from conventional memory cells, and served as precursors of central memory. Antigen-specific TSCM cells preferentially localized to LNs and were virtually absent from mucosal surfaces. They were generated in the acute phase of viral infection, preferentially survived in comparison with all other memory cells following elimination of antigen, and stably persisted for the long term. Thus, one mechanism for maintenance of long-term T cell memory derives from the unique homeostatic properties of TSCM cells. Vaccination strategies designed to elicit durable cellular immunity should target the generation of TSCM cells.