UC San Diego

The transition from naïve to effector CD8+ T cells is marked by metabolic reprograming that requires the interplay of different organelles to maintain cellular homeostasis amid changing intracellular demands and extracellular conditions. Previous studies have demonstrated that peroxisomes have important functions in fatty acid oxidation, regulating reactive oxygen species, and propagating type I interferon signals. However, up to this point, little is known about the importance of this organelle in CD8+ T cells. Thus, this thesis addresses this gap in our understanding of peroxisomes in CD8+ T cell development and function.viii To address this, we generated a mouse model of peroxisome deficient CD8+ T cells and analyzed their development both in-vitro and during acute and chronic lymphocytic chronic meningitis virus (LCMV) infection. Peroxisome-deficient CD8+ T cells behaved identically to wild-type controls in-vitro. However, in-vivo, the lack of this organelle resulted in a significant impairment of their ability to survive beyond day four post-infection. Subsisting peroxisome- deficient CD8+ T cells retained their ability to undergo normal proliferation, function, and differentiation into effector and memory lineages. These results show that peroxisomes are required for viability in-vivo. Further research needs to be conducted to uncover the mechanisms by which peroxisome deficiency is detrimental to CD8+ T cell survival.