Differentiation of human peripheral blood Vδ1 T cells expressing Natural Cytotoxicity Receptors : implications for immunotherapies and the understanding of γδ T cell function

Natural Cytotoxicity Receptors (NCRs) were originally identified as specific natural killer cell activating receptors that, upon binding to their endogenous ligands, trigger the killing of tumor cell targets. Here we describe a population of Vδ1+ T cells from human peripheral blood that can differentiate in vitro to express the NCRs NKp30, NKp44 and NKp46. We show that the expression of NKp30 endows Vδ1+ T cells with the ability to lyse, in vitro, both hematologic tumor cell lines as well as chronic lymphocytic leukemia cells isolated from patients. Moreover, we found that these cells are also able to produce CC chemokines upon the triggering of NKp30, which suppresses HIV-1 viral replication in CD4+ T cells in vitro. This evidence not only further discloses the key role of NK cell receptors in certain γδ T cell functions, but also suggests that Vδ1+ T cells specifically harbor a powerful therapeutic potential through the induction of NCRs, whose function can be manipulated for the treatment of various diseases.