Human KIR+CD8+ T cells target pathogenic T cells in Celiac disease and are active in autoimmune diseases and COVID-19
Li, J.; Zaslavsky, M. E.; Su, Y.; Sikora, M.; van Unen, V.; Christophersen, A.; Chiou, S.-H.; Chen, L.; Li, J.; Ji, X.; Wilhelmy, J.; McSween, A.; Palanski, B. A.; Mallajosyula, V.; Dhondalay, G.; Bhamidipati, K.; Pai, J.; Kipp, L.; Dunn, J.; Hauser, S.; Oksenberg, J.; Satpathy, A.; Robinson, W.; Steinmetz, L.; Khosla, C.; Utz, P.; Sollid, L. M.; Heath, J.; Fernandez-Becker, N.; Nadeau, K.; Saligrama, N.; Davis, M.
Show abstract
Previous reports show that Ly49+CD8+ T cells can suppress autoimmunity in mouse models of autoimmune diseases. Here we find a markedly increased frequency of CD8+ T cells expressing inhibitory Killer cell Immunoglobulin like Receptors (KIR), the human equivalent of the Ly49 family, in the blood and inflamed tissues of various autoimmune diseases. Moreover, KIR+CD8+ T cells can efficiently eliminate pathogenic gliadin-specific CD4+ T cells from Celiac disease (CeD) patients leukocytes in vitro. Furthermore, we observe elevated levels of KIR+CD8+ T cells, but not CD4+ regulatory T cells, in COVID-19 and influenza-infected patients, and this correlates with disease severity and vasculitis in COVID-19. Expanded KIR+CD8+ T cells from these different diseases display shared phenotypes and similar T cell receptor sequences. These results characterize a regulatory CD8+ T cell subset in humans, broadly active in both autoimmune and infectious diseases, which we hypothesize functions to control self-reactive or otherwise pathogenic T cells. One-Sentence SummaryHere we identified KIR+CD8+ T cells as a regulatory CD8+ T cell subset in humans that suppresses self-reactive or otherwise pathogenic CD4+ T cells.
Matching journals
The top 7 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Targeting interferon-{lambda} signaling promotes recovery from central nervous system autoimmunity 96%
- Single-cell profiling of blood and cerebrospinal fluid in tuberculous meningitis 95%
- Protracted yet coordinated differentiation of long-lived SARS-CoV-2-specific CD8+ T cells during COVID-19 convalescence 95%
Similar papers in this journal
- Histone H3K27me3 demethylases regulate human Th17 cell development and effector functions by impacting on metabolism 94%
- T Lymphocyte-Specific Deletion of SHP1 and SHP2 Promotes Activation-Induced Cell Death of CD4+ T Cells and Impairs Antitumor Response 94%
- The dynamic epigenetic regulation of the inactive X chromosome in healthy human B cells is dysregulated in lupus patients 94%
Similar papers in this journal
- T cell activation, highly armed cytotoxic cells and a sharp shift in monocytes CD300 receptors expression is characteristic of patients with severe COVID-19 95%
- TCR repertoire profiling revealed antigen-driven CD8+ T cell clonal groups shared in synovial fluid of patients with spondyloarthritis 95%
- ScRNA-Seq study of neutrophils reveals vast heterogeneity and breadth of inflammatory responses in severe COVID-19 patients 95%
Similar papers in this journal
- Transcriptome network analysis implicates CX3CR1-positive type 3 dendritic cells in non-infectious uveitis 96%
- Compartmentalization and persistence of dominant (regulatory) T cell clones indicates antigen skewing in juvenile idiopathic arthritis 95%
- Neurotrophic factor Neuritin modulates T cell electrical and metabolic state for the balance of tolerance and immunity 94%
Similar papers in this journal
- OCA-B promotes pathogenic maturation 1 of stem-like CD4+ T cells and autoimmune demyelination 96%
- A20's Linear Ubiquitin Binding Motif Restrains Pathogenic Activation of TH17/22 cells and IL-22 Driven Enteritis 94%
- The COVID-19 immune landscape is dynamically and reversibly correlated with disease severity 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.