Immunity & infection
Mitochondria are critical regulators for intracellular signalling, metabolism and apoptosis during T cell activation, differentiation and function. Upon activation, T cells undergo a metabolic shift from oxidative phosphorylation towards aerobic glycolysis, which is obligatory for effector T cell differentiation. We previously showed that the mitochondrial protein TCAIM (T cell activation inhibitor, mitochondrial) controls CD4+ T cell activation and function and demonstrated that Tcaim overexpression inhibits effector/ effector-memory differentiation of conventional CD4+ T cells, thereby, promoting acceptance of allogenic transplants.
We now investigated the role of mitochondria and especially TCAIM for the activation and function of CD8+ T cells isolated from mice with a T cell specific Tcaim overexpression or deletion. Flow cytometry analysis of polyclonal stimulated naïve CD8+ T cells confirmed an inhibitory role of Tcaim expression for CD8+ T cell effector/ effector-memory differentiation and IFN-g production as observed for CD4+ T cells. Interestingly, electron microscopy of naïve and activated CD8+ T cells showed that Tcaim overexpression induced tight cristae formation and prevented mitochondrial fission upon activation whereas deletion of Tcaim caused highly fragmented mitochondria even in naïve cells. This is of particular interest as mitochondrial fission has recently been shown to be crucial for the metabolic shift towards glycolysis, which indeed was abrogated in Tcaim overexpressing cells. Furthermore, co-immunoprecipitation analysis indicated that TCAIM interacts with proteins involved in cristae formation and mitochondrial fusion.
Taken together, our data indicate that the mitochondrial protein TCAIM controls T cell effector/ effector-memory differentiation and function by promoting mitochondrial fusion and cristae formation.