Human KIR+CD8+ T cells target pathogenic T cells in Celiac disease and are active in autoimmune diseases and COVID-19

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.

Does Recombinant Human Bone Morphogenic Protein 2 Affect Perioperative Blood Loss after Lumbar and Thoracic Spinal Fusion?

STUDY DESIGN: Retrospective cohort design. PURPOSE: This study aimed to determine whether recombinant human bone morphogenic protein 2 (rhBMP-2) reduces total perioperative blood loss during lumbar and thoracic fusion. OVERVIEW OF LITERATURE: Previous studies on rhBMP-2 versus iliac crest bone grafting in thoracic and lumbar fusions have yielded mixed results regarding reductions in blood loss and have largely neglected the postoperative period when analyzing total blood loss. Additionally, these studies have been limited by heterogeneity and sample size. METHODS: We analyzed the blood loss patterns of 617 consecutive adult patients undergoing lumbar and/or thoracic fusions requiring subfascial drain placement at a single institution from January 2009 to December 2016. Patients were divided into BMP and non-BMP cohorts, and a propensity score analysis was conducted to account for the differences between cohorts. RESULTS: At a per-level fused basis, the BMP group exhibited a significant reduction in the intraoperative (66.1 mL per-level fused basis; 95% confidence interval [CI], 127.9 to 4.25 mL; p=0.036) and total perioperative blood loss (100.7 mL per-level fused basis; 95% CI, 200.9 to 0.5 mL; p=0.049). However, no significant differences were observed in an analysis when not controlling for the number of levels or when examining the postoperative drain output. CONCLUSION: RhBMP-2 appears to reduce both intraoperative and total blood loss during lumbar and thoracic fusions on a per-level fused basis. This total reduction in blood loss was achieved via intraoperative effects because RhBMP-2 had no significant effect on the postoperative drain output.