title: IL-15 expands unconventional CD8alphaalphaNK1.1+ T cells but not Valpha14Jalpha18+ NKT cells.
abstract: 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 CD8alphaalpha. In contrast to CD4(+)NK1.1(+) T cells, which were mostly CD1d-restricted NKT cells and of which approximately 70% were CD69(+)CD44(+), approximately 70% of CD8(+)NK1.1(+) T cells were CD69(-)CD44(+). We could also expand similar CD8alphaalphaNK1.1(+) T cells but not CD4(+) NKT cells from CD8alpha(+)beta(-) bone marrow cells cultured ex vivo with IL-15. These results indicate that the increased CD8alphaalphaNK1.1(+) T cells are not activated conventional CD8(+) T cells and do not arise from conventional CD8alphabeta precursors. CD8alphaalphaNK1.1(+) 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, CD8alphaalphaNK1.1(+) T cells, and that IL-15-transgenic mice may be a useful resource for studying the functional relevance of CD8(+)NK1.1(+) T cells.
authors.affiliation: Vaccine Branch, National Cancer Institute, National Institute of Health, Bethesda, MD 20893, USA. ytagaya@helix.nih.gov
authors.forename: Masaki
authors.initials: M
authors.lastname: Terabe
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Tagaya
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhu
authors.forename: Larry
authors.initials: L
authors.lastname: Granger
authors.forename: Mario
authors.initials: M
authors.lastname: Roederer
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Waldmann
authors.forename: Jay A
authors.initials: JA
authors.lastname: Berzofsky
mesh_terms: D000818:Animals; D000950:Antigens, Ly; D000954:Antigens, Surface / Q000032:analysis* / Q000276:immunology; D016827:CD8 Antigens / Q000032:analysis* / Q000276:immunology; D015550:Cell Degranulation; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D007156:Immunologic Memory; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D019409:Interleukin-15 / Q000276:immunology* / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D037181:Lectins, C-Type / Q000032:analysis* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D011971:Receptors, Immunologic / Q000032:analysis; D013154:Spleen / Q000166:cytology / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
chemical_list: D000950:Antigens, Ly; D000954:Antigens, Surface; D016827:CD8 Antigens; C409469:CD8 antigen, alpha chain; D016207:Cytokines; D015395:Histocompatibility Antigens Class I; D019409:Interleukin-15; C527211:Klrb1c protein, mouse; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D007371:Interferon-gamma