Résumé
Rare CD1d-αGalCer-specific T cells that do not express the invariant Vα24 chain of human NKT cells were recently identified after expansion in vitro with the lipid antigen, but their phenotype and frequency in vivo and their lineage relationship with NKT cells could not be elucidated. By using a CD1d tetramer-based method to enrich these cells from fresh peripheral blood, we demonstrated their naïve-like CD62Lhigh CD45RO− CD4+ phenotype and their relatively high frequency of ~10−5 in several healthy individuals. Notably, these cells expressed the NKT lineage-specific transcription PLZF, indicating a developmental relationship with NKT cells and ruling out the possibility that they were conventional MHC-restricted T cells crossreacting against CD1d-αGalCer. Although PLZF is known to direct the effector program of NKT cells, we show here that the naïve-like cells expressed it at significantly lower amount than NKT cells. Further, we present mouse studies demonstrating a sharp PLZF expression threshold requirement for induction of the effector phenotype. These findings directly demonstrate in vivo the existence of naïve-like CD1d-restricted human T cells marked by intermediate levels of PLZF.