Clinical and Experimental Sepsis Impairs CD8 T-Cell-Mediated Immunity.

Septic patients experience chronic immunosuppression resulting in enhanced susceptibility to infections normally controlled by T cells. Clinical research on septic patients has shown increased apoptosis and reduced total numbers of CD4 and CD8 T cells, suggesting contributing mechanism driving immunosuppression. Experimental models of sepsis, including cecal ligation and puncture, reverse translated this clinical observation to facilitate hypothesis-driven research and allow the use of an array of experimental tools to probe the impact of sepsis on T-cell immunity. In addition to numerical loss, sepsis functionally impairs the antigen-driven proliferative capacity and effector functions of CD4 and CD8 T cells. Sepsis-induced impairments in both the quantity and quality of T cells results in reduced protective capacity and increased susceptibility of mice to new or previously encountered infections. Therefore, the combined efforts of clinical and experimental sepsis research have begun to elucidate the impact of sepsis on T-cell-mediated immunity and potential T-cell-intrinsic and -extrinsic mechanisms driving chronic immunosuppression. Future work will explore the impact of sepsis on the recently appreciated tissue-resident memory (TRM) T cells, which provide robust protection against localized infections, and dendritic cells, which are needed to activate T cells and promote effective T-cell responses.