A unique lymphotoxin {alpha}beta-dependent pathway regulates thymic emigration of V{alpha}14 invariant natural killer T cells.

Natural killer (NK) T cells using an invariant Vα14 (Vα14i) T cell receptor rearrangement form a distinct immunoregulatory T cell lineage. Several studies indicated that a NK1.1− Vα14i NKT precursor cell differentiates and expands within the thymus before export to the peripheral tissues occurs. However, little is known about the signals that cause the emigration of Vα14i NKT cells from the thymus to the periphery. Here we show that signaling of lymphotoxin (LT) αβ through the LTβ receptor (LTβR) is indispensable for regulating peripheral but not thymic Vα14i NKT cell numbers. Homing to and homeostatic proliferation of thymic Vα14i NKT cells in peripheral organs, however, was not dependent on LTβR. Instead, our data indicate that a LTβR-expressing thymic stromal cell regulates the thymic emigration of Vα14i NKT cells but not conventional T cell receptor αβ cells.