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The Journal of Immunology, 2008, 180, 7276-7286
Copyright © 2008 by The American Association of Immunologists, Inc.

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IL-15 Expands Unconventional CD8{alpha}{alpha}NK1.1+ T Cells but Not V{alpha}14J{alpha}18+ NKT Cells1

Masaki Terabe2,*, Yutaka Tagaya2,{dagger}, Qing Zhu*, Larry Granger{ddagger}, Mario Roederer§, Thomas A. Waldmann{dagger} and Jay A. Berzofsky*

* Vaccine Branch, {dagger} Metabolism Branch, and {ddagger} Experimental Immunology Branch, National Cancer Institute, and § Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892

Despite recent gains in knowledge regarding CD1d-restricted NKT cells, very little is understood of non-CD1d-restricted NKT cells such as CD8+NK1.1+ T cells, in part because of the very small proportion of these cells in the periphery. In this study we took advantage of the high number of CD8+NK1.1+ T cells in IL-15-transgenic mice to characterize this T cell population. In the IL-15-transgenic mice, the absolute number of CD1d-tetramer+ NKT cells did not increase, although IL-15 has been shown to play a critical role in the development and expansion of these cells. The CD8+NK1.1+ T cells in the IL-15-transgenic mice did not react with CD1d-tetramer. Approximately 50% of CD8+NK1.1+ T cells were CD8{alpha}{alpha}. In contrast to CD4+NK1.1+ T cells, which were mostly CD1d-restricted NKT cells and of which ~70% were CD69+CD44+, ~70% of CD8+NK1.1+ T cells were CD69CD44+. We could also expand similar CD8{alpha}{alpha}NK1.1+ T cells but not CD4+ NKT cells from CD8{alpha}+β bone marrow cells cultured ex vivo with IL-15. These results indicate that the increased CD8{alpha}{alpha}NK1.1+ T cells are not activated conventional CD8+ T cells and do not arise from conventional CD8{alpha}β precursors. CD8{alpha}{alpha}NK1.1+ T cells produced very large amounts of IFN-{gamma} and degranulated upon TCR activation. These results suggest that high levels of IL-15 induce expansion or differentiation of a novel NK1.1+ T cell subset, CD8{alpha}{alpha}NK1.1+ T cells, and that IL-15-transgenic mice may be a useful resource for studying the functional relevance of CD8+NK1.1+ T cells.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 This work was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research.

2 Address correspondence and reprint requests to Dr. Masaki Terabe, Vaccine Branch, National Cancer Institute, Building 10, Room 6B-12, 9000 Rockville Pike, National Institutes of Health, Bethesda, MD 20892. E-mail address: terabe{at}mail.nih.gov or Dr. Yutaka Tagaya, Metabolism Branch, National Cancer Institute, Building 10, Room 4B-47, 9000 Rockville Pike, National Institutes of Health, Bethesda, MD 20892. E-mail address: ytagaya{at}helix.nih.gov

3 Abbreviations used in this paper: iNKT cell, NKT cell with invariant TCR {alpha}-chain V{alpha}14J{alpha}18 segment; {alpha}-GalCer, {alpha}-galactosylceramide; KO, knockout; Tg, transgenic; TL, thymic leukemia.




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