Investigating memory CD8 T cell-mediated immunopathology

Abstract Bystander memory CD8 T cells can respond to other pathogens independently of their T cell receptors (TCRs). Current dogma is that these memory CD8 T cells can improve control of unrelated acute infections via TCR independent, innate-like functions. Contrary to this, we observed that mice with memory CD8 T cells with the transgenic P14 TCR that is specific for lymphocytic choriomeningitis virus (LCMV), or P14 memory chimera mice, succumb to a typically sublethal bacterial infection with Listeria monocytogenes (Lm). However, mice with a reduced number of transferred P14 T cells are less susceptible to Lm, suggesting that a high frequency of P14 CD8 T cells leads to increased lethality of Lm infection. At day 3 post Lm infection, LCMV-experienced mice have significantly higher bacterial burdens in the spleen and liver compared to controls. Preliminary data also suggests that certain cytokines may be involved in this process. We are investigating possible mechanisms of bystander memory CD8 T cell-mediated immunopathology. This work highlights that bystander CD8 memory T cells are not unequivocally protective but can also enhance susceptibility to non-cognate infections. Supported by NIH grant, R01 AI38903.