Removal of CD5 and CD6 alters the metabolic and functional profiles of mouse CD4 and CD8 T cells 4139

Abstract Description CD5 and CD6 are immunoregulatory surface receptors found on most mature CD4+ and CD8+ T cells. Previous studies indicate that both receptors attenuate TCR signaling, and their signaling influences the differentiation and memory formation of T cells. Our lab has previously shown that removal of CD5 (CD5KO) alters the metabolic profiles of mouse CD4+ T cells, an aspect of CD5 signaling that has not been extensively explored before. Metabolic pathways, including glycolysis and cellular respiration, play critical roles in the activation and persistence of T cells. In addition to detecting differences in the metabolic profiles of CD5KO, T cells compared to wildtype, we detected increased levels of CD6 on the surface of CD5KO T cells. This suggests that CD6 plays a compensatory role when CD5 is removed. To further investigate the roles of CD5 and CD6 in regulating T cell activation and metabolism, we quantified the activation, differentiation, and metabolic rates of single-knockout (CD5KO and CD6KO) and double-knockout (CD5/6KO) mouse T cells. Our results show that each genotype has its own functional and metabolic profile compared to each other and to wildtype T cells, suggesting that both receptors play roles in regulating the metabolism of T cells in addition to regulating TCR signaling. These findings have implications for T cell therapies as modulating the metabolic profiles of T cells through CD5 and CD6 may enhance the efficacy of these treatments. Funding Sources Simmons Center for Cancer Research at Brigham Young University Topic Categories Immune Response Regulation: Molecular Mechanisms (IRM)