The ability of memory CD8+ T cell subsets to numerically and functionally recover following whole body irradiation is influenced by their history of cognate antigen exposures 2266

Abstract Description As a result of the growing use of nuclear energy and radiation in medical interventions, the risk of radiation exposure among the general public has increased. Exposure to high doses of radiation severely impairs the immune system, including CD8 T cells. While the effects on the naive and primary (1M) memory CD8 T cell pools have been partially characterized, the effect of radiation exposure on CD8 T cell memory generated after repeated Ag exposures has not. Here, we utilized a series of adoptive transfers to generate chimeric mice containing Thy1 distinct 1M and quaternary (4M) P14 CD8 T cells within the same host. 1M and 4M were equally susceptible to radiation-induced cell death. In addition, both cell types showed diminished Ag-driven cytokine production and ability to proliferate upon cognate Ag restimulation in vivo. Despite evidence that 1M and 4M attempt cell cycling in response to the lymphopenic environment, neither group numerically recovers with time. Irradiated 1M and 4M showed decreased expression of key homeostatic cytokine Rc, though expression levels of CD122/CD127 is further diminished in 4M. This, in turn, leads to changes in the composition of memory CD8 T cell compartment in which the representation of 4M is further reduced. Thus, numerical and functional recovery of memory CD8 T cells generated after repeated infections/vaccinations in radiation survivors is severely impaired potentially leaving the host with increased susceptibility to re-infection(s). Topic Categories Lymphocyte Differentiation and Peripheral Maintenance (LYM)