Cutting edge:: Novel priming of tumor-speciftic immunity by NKG2D-triggered NK cell-mediated tumor rejection and Th1-independent CD4+ T cell pathway

NKG2D is an activation receptor on NK cells and has been demonstrated as a primary cytotoxicity receptor for mouse NK cells. Primary rejection of class I-deficient RMA-S lymphoma cells expressing the NKG2D ligand, retinoic acid early inducible-1beta, was critically dependent upon NK cell perform and occurred independently of T cells NKG2D-triggered NK cell rejection of RMA-S-retinoic acid early inducible-1beta tumor primed a secondary tumor-specific T cell response mediated by both CD4(+) and CD8(+) T cells in the effector phase. Surprisingly, during the Priming phase, CD4(+) T cells, but not CD8(+) T cells, were also required to generate this secondary T cell immunity; however, T cell priming was independent of Th1 cytokines, such as IFN-gamma and IL-12. These data imply a novel pathway for priming T cell immunity, that is, stimulated upon NK cell-mediated cytotoxicity of NKG2D ligand-expressing tumor cells, dependent upon CD4(+) T cells in the primary phase, and independent of conventional Th1-type immunity.