IL-15 expands unconventional CD8alphaalphaNK1.1+ T cells but not Valpha14Jalpha18+ NKT cells

J Immunol. 2008 Jun 1;180(11):7276-86. doi: 10.4049/jimmunol.180.11.7276.

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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Antigens, Ly
  • Antigens, Surface / analysis*
  • Antigens, Surface / immunology
  • CD8 Antigens / analysis*
  • CD8 Antigens / immunology
  • Cell Degranulation
  • Cytokines / biosynthesis
  • Cytokines / immunology
  • Histocompatibility Antigens Class I / immunology
  • Immunologic Memory
  • Immunophenotyping
  • Interferon-gamma / biosynthesis
  • Interleukin-15 / immunology*
  • Interleukin-15 / metabolism
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism
  • Lectins, C-Type / analysis*
  • Lectins, C-Type / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • NK Cell Lectin-Like Receptor Subfamily B
  • Receptors, Antigen, T-Cell / immunology*
  • Receptors, Immunologic / analysis
  • Spleen / cytology
  • Spleen / immunology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism

Substances

  • Antigens, Ly
  • Antigens, Surface
  • CD8 Antigens
  • CD8 antigen, alpha chain
  • Cytokines
  • Histocompatibility Antigens Class I
  • Interleukin-15
  • Klrb1c protein, mouse
  • Lectins, C-Type
  • NK Cell Lectin-Like Receptor Subfamily B
  • Receptors, Antigen, T-Cell
  • Receptors, Immunologic
  • Interferon-gamma