Total body sub-lethal irradiation accelerates thymic senescence by reducing lymphoid progenitors in the thymus (HEM7P.236)

Abstract

Abstract Total Body Irradiation (TBI) dramatically damages the BM and thymus organs, however the long-term effects of irradiation and aging on both BM cells and thymocytes are still unclear. In this study, we described that although the kinetics of thymocyte restoration was varied with the sex, dose and exposure age, a long-term and dose dependent reduction of DN1a,b progenitors and a transient over-response peak of thymocytes around 5-6 weeks were shown unanimously in all groups after irradiation, which led to the recovery of thymus maintained in a lower level of total thymocyte number through life. Such events were primarily due to the reduction of functional LSK progenitors in BM rather than the changes to the thymic environment. The damage of irradiation in BM LSK cells was dose dependent and 0.5 Gy was able to result in a significant long-term reduction of LSK progenitors. Responding to the reduction of thymocytes, both DN3 and DN4 subsets played a critical role on the compensation of the reduction of thymocytes with a periodical profile after irradiation, but the recovery potential was dramatically reduced at the age of 12 months. This study provided the evidence that the capability of LSK cells for lymphocyte production in BM is limited and can be dramatically damaged after a single dose of relatively low TBI, which consequently accelerates premature thymic aging and senescence. Our results may also be useful for the evaluation and therapeutic intervention of human TBI events.