Abstract : Recent studies have shown the involvement of neuropilin 1 (Nrp1) in thecontrol of T cell activation, and disruption of this receptor promotes aggravation ofexperimental autoimmune encephalitis (EAE). Through its principal ligand,semaphorin 3A (Sema-3A), Nrp1 appears to participate in an autocrine negativefeedback of T cell proliferation. However, few studies have been conducted inhumans to determine when Nrp1 is expressed by T cells. Here we show thatregulatory T cells (Treg) in humans do not express Nrp1, unlike murine Treg cells. Incontrast, we show that Nrp1 is expressed by effector T cells after engagement withantigen, either in secondary lymphoid organs for follicular helper T cells (Tfh)interacting with B cells, either in peripheral inflammation for effector memory T cells(TEM). We conclude that this expression corresponds to a level of late activation inboth cases and may control T cell activation.The study in mice il2ra-/- revealed a significant role of IL-2 receptor alpha(CD25) for the survival of Treg in vivo, but also for the differentiation of memory Tcells. Only two cases of CD25 deficiency associated with autoimmune diseases havebeen described in humans. However, these studies do not assess at what levelCD25 is involved in T cell homeostasis. Here we provide further insight of thesestudies by presenting three new cases of CD25 deficiency developing autoimmunediseases like IPEX. We show that CD25 plays an active role to maintain naive andeffector Treg cell populations of, and effector memory T cell populations.