Alterations in tissue-resident memory and exhausted-like CD8+ T cells in active UC
Pennsylvania
Abstract
T cells play a central role in the pathogenesis of inflammatory bowel disease (IBD) and represent a key therapeutic target. We analyzed intestinal and peripheral T cells from 116 IBD patients and 29 healthy controls (HC) using CyTOF panels focused on T cell polarization, memory, effector function, homing, and exhaustion. Relative to HC, IBD biopsies showed decreased abundance of CD8+CD69+CD103+ tissueresident memory T cells (TRM) and a concomitant increase in CD8+ T cells that upregulated PD-1 and other markers of T cell exhaustion (TEX-like). We also observed increased abundance of regulatory and conventional CD4+ T cells in IBD relative to HC. TEX-like cells were particularly prominent in active ulcerative colitis where distinct subsets corresponding to terminally differentiated and progenitor-like TEX were evident. Moreover, TEX-like cells retained expression of CD69, a key marker of tissue residence. Importantly, response to therapy was associated with restoration of conventional CD69+CD103+ TRM and downregulation of TEX signatures. Ongoing analyses will define the lineage relationships between TRM and TEX-like cells in IBD.
Biosketch
Lena Mayer holds a medical degree from the RWTH University, Aachen, Germany. In 2015, she completed her doctorate of Medicine at the Institute for Immunology, RWTH University, Aachen. Following that, she started her training as a doctor of Internal Medicine at the University Hospital of Freiburg in the Department of Medicine II. From 2018-2020, she completed a DFG-funded post doc in the Tomov and Wherry labs at the University of Pennsylvania, Philadelphia, USA, focusing on the role of T cells in Inflammatory Bowel Disease. From January 2021, she is continuing her residency and working as a clinician scientist at the Freiburg University Hospital.
Keywords
Inflammatory bowel disease, Tissue residency, T cell exhaustion
Contact
lena.sophie.mayer@uniklinik-freiburg.de
