Requirement for Vα14 NKT Cells in IL-12-Mediated Rejection of Tumors

A lymphocyte subpopulation, the V α 14 natural killer T (NKT) cells, expresses both NK1.1 and a single invariant T cell receptor encoded by the V α 14 and J α 281 gene segments. Mice with a deletion of the J α 281 gene segment were found to exclusively lack this subpopulation. The V α 14 NKT cell–deficient mice could no longer mediate the interleukin-12 (IL-12)–induced rejection of tumors. Although the antitumor effect of IL-12 was thought to be mediated through natural killer cells and T cells, V α 14 NKT cells were found to be an essential target of IL-12, and they mediated their cytotoxicity by an NK-like effector mechanism after activation with IL-12.