UC Merced

Autoimmune diseases comprise more than 80 well characterized disorders that affect 7% of Americans. Cellular and molecular studies of autoimmune disease are extensive, yet few viable long-term treatments exist. Thus, basic research into the cellular and molecular mechanisms underlying autoimmune disease is needed to improve and develop novel treatments. My work seeks to understand the contribution of CD8 T cells and novel CXCR5+ CD8 T cells to autoimmune disease by exploring the mechanisms by which CD8 T cells promote disease. Using a model of systemic autoimmune disease (IL-2Rα-KO), I show that a culmination of factors, including regulatory T cell dysfunction, changes in T cell activation, and differences in cytokine signaling combine to drive disease progression and kinetics. Further, I show that CXCR5+ CD8 T cells localize to the germinal center and B cell follicle, produce cytokines indicative of CD4 T follicular helper (Tfh) cells throughout the B cell follicle, and that CD8-derived IL-4, but not IL-21 impacts B cell function. This work demonstrates that CXCR5+ CD8 T cells share many features with CD4 Tfh cells but may contribute to B cell function through a different combination of mechanisms than CD4 Tfh cells. Future work should assess the contribution of other cytokines and cell surface proteins to CXCR5+ CD8 T cell function, as well as the factors that control the differentiation of this novel subset, particularly in the context of autoimmune disease.