Homeostasis of V alpha 14i NKT cells.

CD1d-reactive natural killer T (NKT) cells with an invariant V alpha 14 rearrangement (V alpha 14i) 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 alpha-galactosylceramide-containing CD1d tetramers to detect V alpha 14i NKT cells, we show here that the expansion of V alpha 14i 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 V alpha 14i 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 CD4(-)CD8(-), resemble those of CD8(+) memory T cells. We propose that this expansion and/or survival in the periphery of V alpha 14i 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 V alpha 14i NKT cell niche.