Cosmc is required for T cell persistence in the periphery

• Type of Material: Article
• Authors: Christopher E. Cutler, Beth Israel Deaconess Medical Center; Mark B. Jones, Beth Israel Deaconess Medical Center; Alicia A. Cutler, University of Colorado; Amanda Mener, Emory University; Connie Arthur, Emory University; Sean Stowell, Emory University; Richard Cummings, Emory University
• Language: English
• Date: 2019-11-01
• Publisher: Oxford University Press, Inc.
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2019. Published by Oxford University Press. All rights reserved.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1093/glycob/cwz054
• Title of Journal or Parent Work: Glycobiology
• Volume: 29
• Issue: 11
• Start Page: 776
• End Page: 788
• Grant/Funding Information: National Institute of Health (P41GM103694, R01AI101982, P01HL085607, U01CA168930 to R.D.C.).
• Keywords: Expression; Recent thymic; O-glycosylation; Antigens; Fate; Glycoproteome; Biochemistry & Molecular Biology; Life Sciences & Biomedicine; O-Glycosylation; Kinetics; Protein glycocsylation; Chaperone; Localization; Cosmc; O-glycans; T cells; Science & Technology
• Research Categories: Biology, Molecular; Chemistry, Biochemistry; Health Sciences, Medicine and Surgery

Abstract

T lymphocytes, a key arm of adaptive immunity, are known to dynamically regulate O-glycosylation during T cell maturation and when responding to stimuli; however, the direct role of O-glycans in T cell maturation remains largely unknown. Using a conditional knockout of the gene (C1GalT1C1 or Cosmc) encoding the specific chaperone Cosmc, we generated mice whose T cells lack extended O-glycans (T cell conditional Cosmc knock out or TCKO mice) and homogeneously express the truncated Tn antigen. Loss of Cosmc is highly deleterious to T cell persistence, with near-complete elimination of Cosmc-null T cells from spleen and lymph nodes. Total T cell counts are 20% of wild type (WT), among which only 5% express the truncated glycans, with the remaining 95% consisting of escapers from Cre-mediated recombination. TCKO thymocytes were able to complete thymic maturation but failed to populate the secondary lymphoid organs both natively and upon adoptive transfer to WT recipients. Our results demonstrate that extended O-glycosylation is required for the establishment and maintenance of the peripheral T cell population.