IL-15 Expands Unconventional CD8ααNK1.1+ T Cells but Not Vα14Jα18+ 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 CD8αα. 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 CD69−CD44+. We could also expand similar CD8ααNK1.1+ T cells but not CD4+ NKT cells from CD8α+β− bone marrow cells cultured ex vivo with IL-15. These results indicate that the increased CD8ααNK1.1+ T cells are not activated conventional CD8+ T cells and do not arise from conventional CD8αβ precursors. CD8ααNK1.1+ T cells produced very large amounts of IFN-γ 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, CD8ααNK1.1+ T cells, and that IL-15-transgenic mice may be a useful resource for studying the functional relevance of CD8+NK1.1+ T cells.