Transplantation preferentially induces a KLRG-1^lo CD127^hi differentiation program in antigen-specific CD8⁺ T cells

Models of infection have shaped our understanding of programmed memory T cell differentiation, yet whether these models apply to memory programming in the context of transplantation has yet to be defined. Previous work has identified differences in the response of antigen-specific CD8⁺ T cells to cognate antigen based on the environment in which the antigen is presented. Thus, we hypothesized that programming of antigen specific CD8⁺ T cells responding to graft and pathogen may be dissimilar. Here we find that antigen-specific CD8⁺ T cells primed by a skin graft contract faster than those primed by gammaherpesvirus (gHV), yet are able to expand more rapidly upon rechallenge. Moreover, graft-primed antigen-specific CD8⁺ T cells exhibited higher frequencies of cells secreting IL-2 and demonstrate lower expression of KLRG-1, which are qualities suggestive of increased recall potential. Additionally, the expression of CD127 at a memory time point suggests graft-elicited CD8⁺ antigen specific T cells are maintained in a less terminally-differentiated state compared to gHV-elicited CD8⁺ antigen specific T cells, despite fewer cells being present at that time point. Taken together, our findings suggest that the surface marker expression and functional profiles of T cells depends on the priming conditions and may be used to predict immunologic risk following transplantation after traditional allosensitization or heterologous immune priming.