Human stem memory T cells (T_SCM) as critical players in the long-term persistence of immune responses

Adaptive immunity relies on the generation of memory lymphocytes from naive precursors of the host immune repertoire (1). To achieve a long-term capacity to respond to natural antigens derived from a broad diverse spectrum of pathogens and tumor cell antigens, the immune system needs to develop special lymphocyte differentiation programs to ensure the perpetuation of a given antigen-specific immune response (1,2). For T lymphocytes, long-lasting immune protection is achieved by the differentiation of naïve T cells upon antigen stimulation events into distinct cell programs consisting of central memory (TCM) and the terminally committed effector memory T cells (TEM). This differentiation model of memory cells is well described for murine models but the translation to human is hampered by the limited sort of immunological compartments studied and the different lifespan of the organisms (3). Although it has been consistently demonstrated that memory T lymphocytes can be present for several years after primary infection or vaccination, little is known about the requirements for long-term persistence of these cells.