A unique lymphotoxin α,β-dependent pathway regulates thymic emigration of Vα14 invariant natural killer T cells

Natural killer (NK) T cells using an invariant V alpha 14 (V alpha 14i) T cell receptor rearrangement form a distinct immunoregulatory T cell lineage. Several studies indicated that a NK1.1(-) V alpha 14i 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 V alpha 14i NKT cells from the thymus to the periphery. Here we show that signaling of lymphotoxin (LT) alpha beta through the LT beta receptor (LT beta R) is indispensable for regulating peripheral but not thymic V alpha 14i NKT cell numbers. Homing to and homeostatic proliferation of thymic V alpha 14i NKT cells in peripheral organs, however, was not dependent on LT beta R. Instead, our data indicate that a LT beta R-expressing thymic stromal cell regulates the thymic emigration of V alpha 14i NKT cells but not conventional T cell receptor alpha beta cells.