Homeostasis of V_α14i NKT cells

CD1d-reactive natural killer T (NKT) cells with an invariant V_α14 rearrangement (V_α14i) 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 V_α14i NKT cells, we show here that the expansion of V_α14i NKT cells in lymphopenic mice was not dependent on CD I d 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_α14i 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_α14i 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_α14i NKT cell niche.