Author(s): Spencer Hess
Mentor(s): K. Scott Weber
Institution BYU
Metabolism is the process cells use to produce the energy and other molecules they need to survive. T-cells are a vital part of the adaptive immune system, and their metabolism affects immune response. When T-cells are activated, their metabolic pathways and products change significantly, as does the function of these cells. Once activated, cells become much more productive and have greater energy needs to kill infected cells, release cytokines, and fight infection. To fulfill these energy needs, they switch from oxidative phosphorylation to glycolysis. Certain receptors on the surface of cells, such as CD5, have been shown to alter T-cell metabolic function after activation. When CD5 is knocked out, the activated cells have higher metabolism and proliferate more. Additionally, activated cells use more metabolites to produce the molecules they need for division, so they sequester more metabolites, lowering blood serum metabolite levels. CD6 is a related receptor involved in the adaptive immune response, whose role in metabolism is not as well understood as CD5. To determine how CD6 affects T cell’s metabolic function we plan on running metabolic profiling assays and looking at metabolite levels, comparing wild type and CD6 KO mice. We will perform metabolic profiling assays to measure mitochondrial stress, glycolysis rate, and oxygen consumption. We will analyze metabolite levels in T-cells and blood serum using gas chromatography-mass spectrophotometry. We hypothesize the knockout will produce a similar effect to the CD5 knockout, increasing metabolic rate and lowering serum metabolites. Understanding this aspect of T-cell metabolism could help develop therapeutics. Treatments that enhance T-cell metabolism could be effective in fighting infections and cancer. Others that suppress the immune response could help treat autoimmune conditions.