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

As a result of the growing use of nuclear energy and radiation in medical interventions within the last decade, the potential for 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 naïve and primary memory (1M) CD8 T cell pools have been partially characterized, the effect of radiation exposure on CD8 T cell memory generated after repeated antigen (Ag) exposures has not. Here, we utilized a series of adoptive transfers to generate chimeric mice containing Thy1 distinct 1M and quaternary memory (4M) P14 CD8 T cells within the same host. We found that 1M and 4M were equally susceptible to radiation-induced cell death early after irradiation. 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 receptors, though expression levels of CD122/CD127 are further diminished in 4M. This, in turn, leads to changes in the composition of the memory CD8 T cell compartment in which the representation of memory CD8 T cells with history of repeated Ag stimulations 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 reinfection(s).