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 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.
Takeda
K
K
Department of Immunology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo 113-8421, Japan.
Hayakawa
Y
Y
Atsuta
M
M
Hong
S
S
Van Kaer
L
L
Kobayashi
K
K
Ito
M
M
Yagita
H
H
Okumura
K
K
D019264:Adoptive Transfer; D000818:Animals; D000941:Antigens / Q000032:analysis*; D000954:Antigens, Surface; D000970:Antineoplastic Agents / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000502:physiology; D018664:Interleukin-12 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000502:physiology*; D037181:Lectins, C-Type; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D055651:NK Cell Lectin-Like Receptor Subfamily B; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D011506:Proteins / Q000032:analysis*
D000941:Antigens; D000954:Antigens, Surface; D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins; C499308:Rag2 protein, mouse; C064655:V(D)J recombination activating protein 2; D018664:Interleukin-12