Normalizing pathogen exposure via pet shop mouse cohousing leads to preferential maintenance of long-lived effector memory CD8 T cells

Abstract

Abstract Studies of the CD8 T cell memory compartment in mice have primarily been done in young mice maintained in specific pathogen free (SPF) environment. The murine compartment is skewed towards central memory CD8 T cells, whereas adult human memory T cells are dominated by effector memory T cells. The murine memory compartment is akin to that of neonate humans, suggesting there are factors missing in SPF mice that are required to mature the T cell compartment. We wanted to ask how pathogen exposure changes the memory compartment of mice, so we utilized a model of pet shop mouse co-housing (COH), which exposes mice to a wide variety of normal mouse pathogens. COH mice display a substantial increase in long-lived effector CD8 T cells (LLEC). LLEC are a CD8 T cell memory population described by the Hamilton Lab that is phenotypically more effector-like and are highly effective at clearing systemic infections when compared to other memory T cells. However, LLEC display reduced homeostatic and antigen-driven proliferation in SPF mice leading to a lower representation in the memory pool. The factors in COH that support LLEC expansion and persistence are currently unknown, and it is also unclear if COH impacts LLEC function. Thus, the goal of this study is to understand what intrinsic and environmental factors contribute to LLEC formation and maintenance, as well as determine how LLEC function contributes to memory responses in COH mice. I have found that COH LLEC are more polyfunctional compared to SPF LLEC, and my preliminary work has found that LLEC turnover is increased in COH mice. Future studies will determine what specific inflammatory cues lead to LLEC expansion, and if this process can be altered to improve T cell responses to infection and vaccination. Supported by grants from the NIH (R01 AI155468)