Epigenetic Maintenance of Acquired Gene Expression Programs during Memory CD8 T Cell Homeostasis

Memory CD8 T cells have a unique ability to provide lifelong immunity against pathogens containing their cognate epitope. Because of their ability to provide lifelong protection, the generation of memory T cells is now a major focus for current vaccination or adoptive cell therapy approaches to treat chronic viral infections and cancer. It is now clear that maintenance of memory CD8 T cells occurs through a process of antigen-independent homeostatic proliferation, which is regulated in part by the gamma chain cytokines IL-7 and IL-15. Here, we will describe the role of these cytokines in the survival and self-renewal of memory CD8 T cells. Further, we will describe the role of epigenetics in the maintenance of acquired functions among memory CD8 T cells during homeostatic proliferation

Beta cell-specific CD8+ T cells maintain stem cell memory-associated epigenetic programs during type 1 diabetes.

The pool of beta cell-specific CD8+ T cells in type 1 diabetes (T1D) sustains an autoreactive potential despite having access to a constant source of antigen. To investigate the long-lived nature of these cells, we established a DNA methylation-based T cell 'multipotency index' and found that beta cell-specific CD8+ T cells retained a stem-like epigenetic multipotency score. Single-cell assay for transposase-accessible chromatin using sequencing confirmed the coexistence of naive and effector-associated epigenetic programs in individual beta cell-specific CD8+ T cells. Assessment of beta cell-specific CD8+ T cell anatomical distribution and the establishment of stem-associated epigenetic programs revealed that self-reactive CD8+ T cells isolated from murine lymphoid tissue retained developmentally plastic phenotypic and epigenetic profiles relative to the same cells isolated from the pancreas. Collectively, these data provide new insight into the longevity of beta cell-specific CD8+ T cell responses and document the use of this methylation-based multipotency index for investigating human and mouse CD8+ T cell differentiation