Identified: a human CD8+ T cell subset that suppresses pathogenic CD4+ T cells in autoimmune and infectious diseases

A subset of CD8+ T cells is increased in the blood and inflamed tissues of patients with a variety of autoimmune diseases and in COVID-19 patients with autoimmune-related complications. Studies in humans and mice suggest that in both species, these regulatory CD8+ T cells (and their mouse equivalent) suppress pathogenic T cells in autoimmune and infectious diseases. Although most CD8+ T cells are geared toward the control of pathogen-infected or cancerous cells, there has been longstanding evidence in mice that a small subset can also suppress autoimmune responses. Ly49+CD8+ T cells are a subset of CD8+ T cells that show immunoregulatory activity in mice. Here, Jing Li et al. report the existence of a similar CD8+ T cell subset in humans; these cells express killer cell immunoglobulin-like receptors (KIRs) and are known as KIR+CD8+ T cells. To date, the suppressive functions of this population of cells have not been clearly defined. Li et al. report that KIR+CD8+ T cells were more abundant in the blood and inflamed tissue of patients with autoimmune conditions like celiac disease, multiple sclerosis, and lupus, as well as in patients infected with influenza virus or SARS-CoV-2. Moreover, in COVID-19 patients, the cells’ presence was associated with autoimmune-related complications. “This suggests that increase of KIR+CD8+ T cells is a general mechanism induced during an infection,” say the authors. In leukocytes of patients with celiac disease, KIR+CD8+ T cells eliminated pathogenic CD4+ T cells. When mice selectively deficient in Ly49+CD8+ T cells were infected with viruses, they showed normal antiviral immune responses but then eventually developed symptoms of autoimmune disease. KIR+CD8+ T cells may therefore be an important therapeutic target for the control of autoimmune diseases following viral infections.