CD8⁺ T Cells You Should Know about in Autoimmunity: Current Paradigms of T Cell Pathogenesis in Autoimmune Disease

CD8 T cells comprise a large portion of cells in inflamed tissues in many autoimmune diseases, yet their roles in autoimmune pathogenesis have been unclear.

Newer studies have demonstrated that CD8 T cells perform many effector functions that may play a vital role in autoimmune disease pathogenesis. In some autoimmune diseases, such as type 1 diabetes and polymyositis, classical cytotoxic T lymphocytes are thought to play a driving role, but in most tissues affected by autoimmune disease, granzyme K-expressing CD8 T cells are the most abundant. These cells have low cytotoxic potential and instead stimulate nearby cells by releasing cytokines and granzyme K, which can activate complement cascades. Resident memory CD8 T cells are also present in autoimmune tissues, although their roles in pathogenesis are less clear. Foxp3⁺ CD8 T cells exist, but regulatory functions of CD8 T cells extend beyond this population, as CD39 and GzmB expressed by other CD8 T cell subsets can suppress or kill nearby antigen-presenting cells and other pro-inflammatory cells. In this review, we describe CD8 T cell subsets and functions, their associations with human autoimmune diseases, as well as current and in-development treatments that target CD8 T cells.