Critical role of NK1+ T cells in IL-12-induced immune responses in vivo.
CD1-dependent NK1+ T cells rapidly produce IL-4 upon stimulation through the TCR. These cells may therefore play an important role in the initiation of Th2 responses. Here, we show that NK1+ T cells constitutively express receptors for IL-12 and IFN-gamma, and that IL-12 induces production of perforin in these cells. Moreover, while IL-12 induces high levels of IFN-gamma and cytotoxic activity of hepatic or splenic mononuclear cells against tumor cells, this effect of IL-12 is significantly reduced in CD1-deficient mice with impaired NK1+ T cells development. These results indicate that NK1+ T cells play a critical role in IL-12-induced production of IFN-gamma to initiate Th1 immune responses and as IL-12-induced cytotoxic effector cells to initiate antitumor immunity.
Kawamura
T
T
Department of Immunology, Niigata University School of Medicine, Japan.
Takeda
K
K
Mendiratta
S K
SK
Kawamura
H
H
Van Kaer
L
L
Yagita
H
H
Abo
T
T
Okumura
K
K
D000818:Animals; D000941:Antigens / Q000032:analysis*; D018949:Antigens, CD1 / Q000502:physiology; D000954:Antigens, Surface; D003602:Cytotoxicity, Immunologic; D053222:Fas Ligand Protein; D018664:Interleukin-12 / Q000494:pharmacology*; D037181:Lectins, C-Type; D008099:Liver / Q000166:cytology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055651:NK Cell Lectin-Like Receptor Subfamily B; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D011506:Proteins / Q000032:analysis*; D017471:Receptors, Interferon / Q000378:metabolism; D018123:Receptors, Interleukin / Q000378:metabolism; D053707:Receptors, Interleukin-12; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D015854:Up-Regulation; D000096743:Interferon gamma Receptor
D000941:Antigens; D018949:Antigens, CD1; D000954:Antigens, Surface; D053222:Fas Ligand Protein; D018664:Interleukin-12; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D055651:NK Cell Lectin-Like Receptor Subfamily B; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D011506:Proteins; D017471:Receptors, Interferon; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D000096743:Interferon gamma Receptor; C505658:Fasl protein, mouse