CD4+ CD44v.low cells are unique peripheral precursors that are distinct from recent thymic emigrants and stem cell-like memory cells

CD4+ CD44v.low cells are peripheral precursor T cells that inhibit lymphopenia by generating a large CD4+ T cell pool containing balanced numbers of naive, memory, and regulatory Foxp3+ cells with a diverse TCR repertoire. Recent thymic emigrants (RTE) and stem cell-like memory T cells (TSCM) can also replenish a T cell pool. In this study we formally test whether CD44v.low cells are the same population as RTE and TSCM. Our data show that, in contrast to RTE, CD44v.low cells express high levels of CD45RB and low levels of CD24. Moreover, CD44v.low cells isolated from mice devoid of RTE retain their capacity to repopulate lymphopenic mice with naive and memory cells and Foxp3+ Tregs. In addition, CD44v.low cells do not express IL-2Rβ, Sca-1, and CXCR3, the phenotypic hallmarks of TSCM. Overall, these data demonstrate that CD44v.low cells are neither RTE nor TSCM.