Gopal Krishna Ramadas Dhondalay PhD

Project | 21

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KIR+CD8+ T cells suppress pathogenic T cells and are active in autoimmune diseases and COVID-19

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Summary

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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. To address these investigations, we used scRNA-seq analysis of total CD8+ T cells from the blood of HCs (N = 10), MS patients (N = 6), and COVID-19 patients (N = 25) by 10X Genomics. UMAP plot of the eight subpopulations identified by unsupervised clustering, Seurat, UMAP plots and other visualisation tools.

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A publication in the journal of Science was published related to this project.

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