The chemokine receptor CxCR3 retains invariant natural killer T cells in the thymus (134.21)

Abstract

Invariant Natural Killer T (iNKT) cells are characterized by expression of a semi-invariant Vα14-Jα18 TCRα chain and NK lineage markers such as NK1.1. In the thymus, iNKT cell maturation coincides with NK1.1 up-regulation and paradoxically, the retention of the mature NK1.1+ subset. The signals involved in the retention of iNKT cells remain undefined. Here, we report that upregulation of the chemokine receptor CxCR3 on thymic iNKT cells serves to retain them in the thymus of adult mice. Strikingly, genetic deletion or neutralization of CxCR3 results in leakage of thymic iNKT cells into the peripheral circulation. These results suggest an unexpected role for CxCR3 in thymic iNKT cell homing and localization patterns.