Relative contribution of NK and NKT cells to the anti-metastatic activities of IL-12

Conventional T cells, NK cells and NKT cells have been implicated in the an ti-tumor activities induced by IL-12, Here we show that IL-12-induced immun e responses are partially impaired in T and NKT cell-deficient RAG-2(-/-) m ice, and in NKT cell-deficient CD1(-/-) mice. In response to a small dose ( <1000 U) of IL-12, RAG-2(-/-) and CD1-/- mice demonstrated reduced cytotoxi city, serum IFN-gamma elevation and anti-metastatic activities; in contrast , in response to a high dose (>2000U) of IL-12, the IL-12-induced immune re sponses of RAG-2(-/-) and CD1(-/-) mice were indistinguishable from wildtyp e mice. The defective responses to low-dose IL-12 of RAG-2(-/-) mice were c orrected by adoptive transfer of NKT cells but not NK cells. These findings indicate that both NK and NKT cells contribute to the anti-metastatic resp onses induced by IL-12, and that NKT cells are mostly responsible for the l ow-dose activities of this cytokine.