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In this work, we find that CD8 + T cells expressing inhibitory killer cell immunoglobulin-like receptors (KIRs) are the human equivalent of Ly49 + CD8 + regulatory T cells in mice and are increased in the blood and inflamed tissues of patients with a variety of autoimmune diseases. Moreover, these CD8 + T cells efficiently eliminated pathogenic gliadin-specific CD4 + T cells from the leukocytes of celiac disease patients in vitro. We also find elevated levels of KIR + CD8 + T cells, but not CD4 + regulatory T cells, in COVID-19 patients, correlating with disease severity and vasculitis. Selective ablation of Ly49 + CD8 + T cells in virus-infected mice led to autoimmunity after infection. Our results indicate that in both species, these regulatory CD8 + T cells act specifically to suppress pathogenic T cells in autoimmune and infectious diseases.

Single-cell analysis is a powerful technology that has found widespread use in recent years. For diseases with involvement of adaptive immunity, single-cell analysis of antigen-specific T cells and B cells is particularly informative. In autoimmune diseases, the adaptive immune system is obviously at play, yet the ability to identify the culprit T and B cells recognizing disease-relevant antigen can be difficult. Celiac disease, a widespread disorder with autoimmune components, is unique in that disease-relevant antigens for both T cells and B cells are well defined. Furthermore, the celiac disease gut lesion is readily accessible allowing for sampling of tissue-resident cells. Thus, disease-relevant T cells and B cells from the gut and blood can be studied at the level of single cells. Here we review single-cell studies providing information on such adaptive immune cells and outline some future perspectives in the area of single-cell analysis in autoimmune diseases., (© 2021. The Author(s), under exclusive licence to Society for Mucosal Immunology.)

In this work, we find that CD8+ T cells expressing inhibitory killer cell immunoglobulin-like receptors (KIRs) are the human equivalent of Ly49+CD8+ regulatory T cells in mice and are increased in the blood and inflamed tissues of patients with a variety of autoimmune diseases. Moreover, these CD8+ T cells efficiently eliminated pathogenic gliadin-specific CD4+ T cells from the leukocytes of celiac disease patients in vitro. We also find elevated levels of KIR+CD8+ T cells, but not CD4+ regulatory T cells, in COVID-19 patients, correlating with disease severity and vasculitis. Selective ablation of Ly49+CD8+ T cells in virus-infected mice led to autoimmunity after infection. Our results indicate that in both species, these regulatory CD8+ T cells act specifically to suppress pathogenic T cells in autoimmune and infectious diseases.