Homeostasis of Vα14i NKT cells

Abstract

CD1d-reactive natural killer T (NKT) cells with an invariant Vα14 rearrangement (Vα14i) are a distinct subset of T lymphocytes that likely have important immune-regulatory functions. Little is known regarding the factors responsible for their peripheral survival. Using α-galactosylceramide–containing CD1d tetramers to detect Vα14i NKT cells, we show here that the expansion of Vα14i NKT cells in lymphopenic mice was not dependent on CD1d expression and was unaffected by the presence of host NKT cells. Additionally, we found that IL-15 was important in the expansion and/or survival of Vα14i NKT cells, with IL-7 playing a lesser role. These results demonstrate that the homeostatic requirements for CD1d-restricted NKT cells, which are CD4+ or CD4CD8, resemble those of CD8+ memory T cells. We propose that this expansion and/or survival in the periphery of Vα14i NKT cells is affected by competition for IL-15, and that IL-15–requiring cells—such as NK cells and CD8+ memory cells—may define the Vα14i NKT cell niche.

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Figure 1: Vα14i T cell proliferation in a lymphopenic environment.
Figure 2: The NKT cell niche and CD1d requirement for proliferation.
Figure 3: Vα14i T cell deficiencies in cytokine-deficient mice.
Figure 4: Analysis of developmental intermediates of Vα14i T cells in cytokine- deficient mice.
Figure 5: Response of Vα14i T cells to IL-15 in vitro and in vivo.
Figure 6: Turnover of peripheral Vα14i T cells in IL-15−/− mice.
Figure 7: Proliferation of Vα14i T cells in cytokine-deficient mice.
Figure 8: Competition of other cell types with Vα14i T cells for IL-15 in vitro and in vivo.

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Acknowledgements

We thank G. Kim and J. Sprent for helpful discussions, H. Cheroutre for critical reading of the manuscript and TSRI for help with cell sorting. Supported by NIH grants CA52511 (to M. K.) and AI45809 (to C. D. S.) and a grant from the Human Frontiers of Science Research Program (to M. K.). L. G. is supported by the Cancer Research Institute, W. C. K. is supported by U.S. Public Health Service Institutional National Research Service Award AI07244, J. T. T. is supported by US Public Health Service Institute National Research Service Award H07196 and C. D. S. is supported by the Leukemia and Lymphoma Society.

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Correspondence to Mitchell Kronenberg.

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Matsuda, J., Gapin, L., Sidobre, S. et al. Homeostasis of Vα14i NKT cells. Nat Immunol 3, 966–974 (2002). https://doi.org/10.1038/ni837

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