Down-regulation of tumoricidal NK and NK T cell activities by MHC Kb molecules expressed on Th2-type γδ T and αβ T cells coinfiltrating in early B16 melanoma lesions

We examined whether gamma delta T and alpha beta T cells accumulating in early B16 melanoma lesions regulate NK and NK T cells that attack tumor cells. Freshly isolated and cultured tumor-infiltrating lymphocyte (TIL) populations of NK and NK T cells lysed B16 and produced IFN-gamma, whereas gamma delta T and a large part of cup T cell populations had no substantial cytotoxicity against BIG and secreted Th2 cytokines, Furthermore, the freshly isolated NK1.1(+) TIL population exhibited a higher anti-B16 effect than did splenocytes. gamma delta T and alpha beta T cell populations dramatically inhibited the cytotoxicity of NK and NK T cells in an MHC K-h-dependent manner. Culture supernatant from gamma delta T and cup T cell populations inhibited the proliferation of NK and KK T cell populations but did not affect their cytotoxicity, suggesting that the released Th2 cytokines are merely partly involved in the down-modulation of NK-lineage cells. NK1.1(+) cells obtained from TIL of gamma delta T cell-depleted mice significantly lysed B16 cells compared with those from control mice. Finally, anti K-b Fab mAb injected intralesionally at an early, but not at a late, stage of development of B16 melanoma inhibited tumor growth. These findings suggest that Th2-type gamma delta T and alpha beta T cells infiltrating in early B16 development inhibit the tumoricidal activity of NK-lineage cells using their class I molecules and partly their suppressive cytokines.