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

Takeda K, Hayakawa Y, Atsuta M, Hong S, Van Kaer L, Kobayashi K, Ito M, Yagita H, Okumura K
Int Immunol. 2000 12 (6): 909-14

PMID: 10837418 · DOI:10.1093/intimm/12.6.909

Conventional T cells, NK cells and NKT cells have been implicated in the anti-tumor activities induced by IL-12. Here we show that IL-12-induced immune responses are partially impaired in T and NKT cell-deficient RAG-2(-/-) mice, 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 cytotoxicity, serum IFN-gamma elevation and anti-metastatic activities; in contrast, in response to a high dose (>2000 U) of IL-12, the IL-12-induced immune responses of RAG-2(-/-) and CD1(-/-) mice were indistinguishable from wild-type mice. The defective responses to low-dose IL-12 of RAG-2(-/-) mice were corrected by adoptive transfer of NKT cells but not NK cells. These findings indicate that both NK and NKT cells contribute to the anti-metastatic responses induced by IL-12, and that NKT cells are mostly responsible for the low-dose activities of this cytokine.

MeSH Terms (15)

Adoptive Transfer Animals Antigens Antigens, Surface Antineoplastic Agents DNA-Binding Proteins Interleukin-12 Killer Cells, Natural Lectins, C-Type Male Mice Mice, Inbred C57BL Neoplasm Metastasis NK Cell Lectin-Like Receptor Subfamily B Proteins

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