Activated memory T cells cross-talk to naïve T cells: A mechanism for generation of autoreactive T cells

Abstract Cytotoxic CD8 T cells (CTLs) can be auto-reactive under certain environmental and genetic conditions resulting in a wide range of autoimmune diseases. Although, these cells are detected at a very low frequency in healthy subjects, the mechanism(s) responsible for their maintenance/generation is not completely understood. Previously, we demonstrated that activated/memory CD8 T cells influence the fate of autologous naïve CD8 T cells acquiring activated/memory phenotype, suggesting that these cells might be auto-reactive. Since both CD4 and CD8 T cells play a pivotal role in the pathogenesis of autoimmune diseases, we examined whether their interaction could contribute to generation of auto-reactive T cells. Here, we showed that CD8 naive cells acquired activated-memory phenotype (CCR7neg CD45RO+) in the presence of activated memory CD4 T cells. Further using Type I diabetes (T1D) tetramers, we observed ~4% of these cells are autoreactive. These findings revealed a possible mechanism where activated memory CD4 T cells are capable to communicate with CD8 naive cells and generate auto-reactive T cells, which may have implications of autoimmunity following vaccination and transplantation.