Immunophenotyping and Functional Assessment of Antiviral CD8+ T Cells in a CLP Mouse Model of Immunosuppression
Abstract
Sepsis causes millions of deaths every year with 70% of them being attributed to the immunosuppressive phase of the syndrome, which occurs shortly after the onset and leads to a severe immunodeficiency. Currently, there is not enough known about antigen specific CD8+ T cell responses during the immunosuppressive phase of sepsis and the studies that have been done, have shown controversial findings. In my thesis research, I have utilized the cecal ligation and puncture (CLP) model of polymicrobial sepsis – which closely mimics the progression of human sepsis – to study antigen specific CD8+ T cell responses by examining their exhaustion phenotype and functionality. Contrary to my initial thoughts, I had discovered that primary and recall CD8+ T cell responses are enhanced during protracted sepsis within the spleen. I demonstrated that antigen specific CD8+ T cells were higher in frequency within the septic spleen; however, they possessed similar absolute numbers compared to the sham control. Additionally, these antigen specific CD8+ T cells had an increased functionality as demonstrated by their increased ability to produce IFN-gamma and granzyme B, while maintaining their polyfunctionality. Furthermore, I also discovered that antigen specific CD8+ T cells within the septic spleen were phenotypically more exhausted as these cells had an enhanced co-expression of the different exhaustion markers examined. Herein, I conclude that sepsis-induced immunosuppression leads to an enhanced antigen specific CD8+ T cell response within the spleen, which is an important finding as it currently contrasts the commonly thought notion that CD8+ T cell responses are dampened during protracted sepsis. This research may alter the way we think about sepsis-induced immunosuppression as I have shown that antigen specific CD8+ T cell responses were enhanced, rather than dampened.