CD5 expression influences T cell metabolism and mice behavior

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Abstract T cells are key players in the adaptive immune response and undergo metabolic changes upon activation. CD5 is a co-receptor found on T cells and plays a significant role in regulating T cell thymic development, intracellular signaling and cytokine production. Previous studies have found that naïve T cells with high CD5 expression (CD5hi) have increased TCR signal strength and enhances immune response to foreign peptide in the periphery. Additionally, we have reported that CD5hi naïve T cells have higher calcium mobilization and improved T cell activation compared to CD5lo T cells. Calcium influx levels can modulate and influence metabolic changes in T cells. Thus, we hypothesized that CD5hi, CD5lo and CD5 deficient T cells have different bioenergetic demands that affect metabolic pathways and T cell activation. We evaluated the effects of CD5 levels on metabolism using CD5 deficient mice vs wild type controls and found CD5 deficient T cells had significant differences in metabolic function. Recently published work has described a connection between increased T cell metabolism and altered cognitive function in PD-1 deficient mice. We have also found significant differences between CD5 deficient and wild type mice in marble burying rates, elevated plus and water maze behavior and open field activity. These behavioral test results suggest CD5 deficient mice have altered cognitive function and higher levels of anxiety. Thus, CD5 deficiency alters T cell metabolic and cognitive function.