SEX SPECIFIC DIFFERENCES IN THE GENOMIC LANDSCAPES OF NAÏVE MALE AND FEMALE CD8+ T-CELLS
Sex specific differences in the immune response have been demonstrated in organisms from sea urchins to humans. In mammals, these differences have been linked to processes in both the innate and adaptive immune responses, and many autoimmune disorders (e.g. systemic lupus erythematosus, rheumatoid arthritis, thyroid disease) show a bias towards developing in females. However, the complex mechanisms behind these discrepancies are not fully understood. CD8+ T-cells are a subtype of lymphocytes that are critical to the production of and response to inflammatory signaling, so they are likely to play a role in these autoinflammatory processes. Previous work in murine naïve CD8+ T-cells has shown that naïve female CD8+ T-cells follow different patterns of differentiation after antigen exposure than male CD8+ T-cells. Both sexes form the same number of differentiated cells, but the ratio of T-cell subsets formed differs between males and females. Female CD8+ T-cells tend to differentiate into short-lived effector cells (SLECs) that respond directly to invaders and produce large amounts of inflammatory cytokines, while their male counterparts tend to differentiate into memory precursor effector cells (MPECs) that respond less directly to infection but can transition into the pool of cells that forms immunological memory. Co-transfer experiments and assays of T-cell function suggest that this altered differentiation may be cell intrinsic, as opposed to being a product of different niches between males and females. To investigate the potential genomic factors driving sex specific differences in CD8+ T-cell differentiation, I performed RNA-seq and PRO-seq on naïve male and female CD8+ cells. These data revealed a potential role for the Type I Interferon response and the related transcription factor IRF7 in the differentiation of female naïve CD8+ T-cells. Future investigations will be required to elucidate the exact mechanism of this differential expression of the Type I IFN pathway.
Grimson, Andrew William
Alani, Eric E.
Biochemistry, Molecular and Cell Biology
M.S., Biochemistry, Molecular and Cell Biology
Master of Science
dissertation or thesis