TCR Repertoire Analysis Quantifies Effect of Irradiation on Homeostasis of iNKT Cell Development in the Thymus of Mice.

Thymic T cell development shows homeostasis against various stressors. Invariant natural killer T (iNKT) cells in the thymus contribute to recovery of thymic development after irradiation owing to their initial tolerance to irradiation compared to conventional thymocytes. However, whether and how iNKT cell development recovers from irradiation remains unknown. Here we show that iNKT cells in the thymus exhibit much slower postirradiation recovery than conventional thymocytes. We observed that fluctuation of V and J genes usage does not correlate with the decrease of iNKT cell population and that irradiation markedly elevated the frequency of cell death relative to proliferation in iNKT cells. Mathematical modeling of recovery dynamics of iNKT cell progenitors implied that lack of rapid proliferation immediately after irradiation, unlike conventional thymocytes, contributes to the prolonged reduction of iNKT cell population. These findings indicate that the development of iNKT cells is subject to long-term effects of irradiation which leads to an increased rate of cell death and raise the possibility of an association between the prolonged reduction of iNKT cells after irradiation and autoimmune diseases caused by irradiation in bone marrow transplantation.