TCRαβ+ CD8αα+ intestinal intraepithelial lymphocytes (CD8αα IELs) are an abundant population of thymus-derived T cells that protect the gut barrier surface. We sought to better define the thymic IEL precursor (IELp) by analysis of their maturation, localization, and emigration. We defined two precursors among TCRβ+CD4–CD8– thymocytes using TAK1 dependence and rigorous lineage-exclusion criteria. Those IELp populations include a nascent PD-1+ population and a T-bet+ population that accumulated with age. Both gave rise to intestinal CD8αα IELs upon adoptive transfer. PD-1+ cells contained more strongly self-reactive clones and were largely classical MHC restricted. They localized to the cortex, and efficiently emigrated in an S1PR1-dependent manner. T-bet+ IELp localized to the medulla, included non-classical MHC-restricted cells and expressed NK1.1, CD103 and CXCR3. The two IELp populations further differed in TCR Vα and Vβ usage. These data provide an important foundation for understanding the biology of CD8αα IELs.

No abstract

No abstract

Background Patients with severe SARS-CoV-2 infection have been shown to have abnormal coagulation parameters and are at increased risk of thromboembolism. The optimal thromboprophylaxis regimen that minimizes thrombosis without increased risk of serious bleeding is uncertain. Objectives To describe the efficacy and safety of increased intensity (enhanced) thromboprophylaxis in patients with COVID-19 admitted to the medical intensive care unit (MICU). Methods This is a retrospective cohort analysis of patients with a diagnosis of COVID-19 admitted to the MICU of an urban safety net hospital. With the exception of patients being supported with extracorporeal membrane oxygenation or on chronic anticoagulation who received therapeutic dosing of anticoagulation, thromboprophylaxis was given as either enoxaparin or unfractionated heparin in doses higher than those recommended for standard prophylaxis, but lower than those used for therapeutic anticoagulation. Main results Of the 120 patients managed with an enhanced thromboprophylaxis protocol, 6 (5%) experienced thromboembolism as a result of their COVID-19 disease (1 pulmonary embolus, 4 deep vein thromboses, and 1 arterial embolism). Four patients experienced major bleeding while receiving therapeutic anticoagulation. Conclusions In critically ill patients with COVID-19, increased intensity (enhanced) thromboprophylaxis appears to be effective at preventing clinically significant thromboembolic events without an increased risk of serious bleeding.

No abstract