Delineation of naïve CD8+ T cell loss and reconstitution following exposure to sublethal whole-boy irradiation

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Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B740
Abstract ID: 5215

Presenting Author:
Mohammad Heidarian , Graduate Research Assistant at Univ. of Iowa Carver Col. of Med.

Abstract:

While the immunosuppressive effect of ionizing radiation (IR) is commonly used as a conditioning regimen of hematopoietic stem cell transplants, delayed immune reconstitution, mainly lymphocytes, remains a leading cause of morbidity and mortality. We have previously shown that memory CD8+ T (T_MEM) lymphocytes, potent mediators of anti-tumor and intracellular re-infections, are permanently lost and exhibit subpar functionality long after sublethal whole-body irradiation (WBI). However, the long-term impact of WBI on naïve CD8+ T (T_N) cells, a key component of immune response to new intracellular pathogens, remains poorly understood. Using P14 LCMV immune chimeric mice, we observed that although T_N cells are more susceptible to radiation-induced cell loss than bona-fide T_MEM cells, the number of T_N cells gradually recovered in a thymus-dependent manner. Profiling the T cell receptor (TCR) beta-chain repertoire within total T_N cells revealed altered TCR clonotype composition and diversity in lymphoreplete irradiated hosts. Additionally, the numerical recovery of T_N cells was concomitant with an increased representation of virtual memory phenotype (CD11a^hi, CD49d^lo, CD62L^hi) in total and GAP50_41-48, B8R_20-27, and GP_33-41 epitope-specific CD8+ T cells. Together, these data demonstrate lasting numerical and phenotypical changes to the T_N compartment, which may influence the breadth of primary immune responses to newly encountered antigens or infections.