Homeostasis of Vα14i 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.