Relative contribution of NK and NKT cells to the anti-metastatic activities of IL-12 |
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Authors: | Takeda K Hayakawa Y Atsuta M Hong S Van Kaer L Kobayashi K Ito M Yagita H Okumura K |
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Affiliation: | Department of Immunology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo 113-8421, Japan. |
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Abstract: | 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. |
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Keywords: | anti-metastatic activity IL-12 NK cell NKT cell |
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