NKT cells act as regulatory cells rather than killer cells during activation of NK cell-mediated cytotoxicity by alpha-galactosylceramide in vivo.
Administration of NKT cell ligands, alpha-galactosylceramide (alpha-GalCer) resulted in the activation of both cytokine production and natural killing. These responses were abolished in both CD1d-deficient mice and Valpha14NKT-deficient mice. Therefore, NKT cells have been considered to be responsible cells for both cytokine production and natural killing. Here, we reevaluated a critical role of NKT and NK cells at early time after alpha-GalCer administration. Intracellular staining experiments demonstrated that NKT cells were the earliest source of both IL-4 and IFN-gamma production after alpha-GalCer administration in vivo. However, these alpha-GalCer-activated NKT cells exhibited no significant natural killing activity. In contrast, isolated NK1.1+CD3- classical NK cells exhibited greatly enhanced natural killing activity 6 h after alpha-GalCer administration. NKT cells, however, exhibited a strong cytotoxicity when they were activated and expanded with alpha-GalCer plus IL-2 in vitro. These results indicated that NKT cells act as regulatory cells via production of cytokines for activation of NK cell-mediated cytotoxicity in vivo at early phase after alpha-GalCer administration. Thus, NK cells rather than NKT cells may be a crucial early activated killer induced by alpha-GalCer in vivo.
Division of Immunoregulation, Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, N-15, W-7, Sapporo 060-0815, Japan.
Kenji
K
Chamoto
Tsuguhide
T
Takeshima
Akemi
A
Kosaka
Takemasa
T
Tsuji
Junko
J
Matsuzaki
Yuji
Y
Togashi
Hiroaki
H
Ikeda
Takashi
T
Nishimura
D000818:Animals; D003602:Cytotoxicity, Immunologic; D005699:Galactosylceramides / Q000494:pharmacology*; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology*; D008024:Ligands; D008213:Lymphocyte Activation; D051379:Mice; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D005699:Galactosylceramides; D008024:Ligands; C493154:alpha-galactosylceramide; D015847:Interleukin-4; D007371:Interferon-gamma