TCR V-ALPHA-24 AND V-BETA-11 COEXPRESSION DEFINES A HUMAN NK1 T-CELL ANALOG CONTAINING A UNIQUE TH0 SUBPOPULATION

Murine NK1 natural T (NT) cells are a population of alpha beta T cells that express NK cell receptors and an invariant TCR rearrangement. Th ese cells rapidly produce large amounts of IL-4 upon activation and ha ve been suggested to promote Th2 differentiation. We sought to determi ne whether a human NK1 T cell analogue could be detected in PBMC, and if so, characterize the TCR usage, cytokine expression, and surface ph enotype of this subset. Using flow cytometry, we have demonstrated a d istinct population of V alpha 24(+), V beta 11(+), CD56(+) T cells con sistent with NT cells. Upon sequencing these cells expressed an invari ant V alpha 24-J alpha Q TCR rearrangement, verifying their identity a s a human NK1 T cell analogue. NT cells demonstrated increased frequen cies of both IFN-gamma and IL-4 production. Strikingly, 30 to 45% of C D4(+) NT cells expressed IL-4, a sixfold greater frequency than that s een in mainstream CD4(+) alpha beta T cells. Contrary to the pattern s een with mainstream T cells, virtually all IL-4-producing NT cells coe xpressed IFN-gamma, indicating that this subset of NT cells has a uniq ue Th0 phenotype. These data establish that V alpha 24(+) NT cells are a potent source of IL-4 and as such, may play a role in Th2 priming i n human immune responses. This work demonstrates that human NT cells c an be phenotypically identified and functionally studied in the blood of healthy or diseased subjects.