Critical role of NK but not NKT cells in acute rejection of parental bone marrow cells in F1 hybrid mice.

F1 hybrid mice vigorously reject transplanted parental bone marrow (BM) cells, which is a phenomenon called "hybrid resistance (HR)". Since NK1.1(+) cells play crucial role in HR, both NK1.1(+)CD3(+) NKT cells and NK1.1(+)CD3(-) NK cells have been possible candidates of effector cells. To elucidate the major effector cells in HR, we employed Rag-2(-/-) mice devoid of T, B, and NKT cells and cytokine receptor common gamma subunit and Rag-2 double-deficient (gamma(c)(-/-(y))-Rag-2(-/-)) mice lacking all lymphoid cells including NK cells. Rag-2(-/-) F1 hybrid mice rejected parental BM cells to the extent similar to wild-type (WT) F1 hybrids. In contrast, male gamma(c)(-/y)-Rag-2(-/-) F1 hybrid mice were unable to reject parental BM cells. After reconstitution with NK but not NKT cells, male gamma(c)(-/y)-Rag-2(-/-) F1 hybrid mice restored the ability to reject parental BM cells. Collectively, it is concluded that NKT cells play little role, if any, and NK cells are the only cells involved in HR.