title: Glycoantigens induce human peripheral Tr1 cell differentiation with gut-homing specialization.
abstract: The carbohydrate antigen (glycoantigen) PSA from an intestinal commensal bacteria is able to down-regulate inflammatory bowel disease in model mice, suggesting that stimulation with PSA results in regulatory T cell (Treg) generation. However, mechanisms of how peripheral human T cells respond and home in response to commensal antigens are still not understood. Here, we demonstrate that a single exposure to PSA induces differentiation of human peripheral CD4(+) T cells into type-Tr1 Tregs. This is in contrast to mouse models where PSA induced the production of Foxp3(+) iTregs. The human PSA-induced Tr1 cells are profoundly anergic and exhibit nonspecific bystander suppression mediated by IL-10 secretion. Most surprisingly, glycoantigen exposure provoked expression of gut homing receptors on their surface. These findings reveal a mechanism for immune homeostasis in the gut whereby exposure to commensal glycoantigens provides the requisite information to responding T cells for proper tissue localization (gut) and function (anti-inflammatory/regulatory).
authors.affiliation: Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
authors.forename: Lori S C
authors.initials: LS
authors.lastname: Kreisman
authors.forename: Brian A
authors.initials: BA
authors.lastname: Cobb
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology* / Q000378:metabolism; D024201:Bystander Effect / Q000276:immunology; D002241:Carbohydrates / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology*; D006706:Homeostasis / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology* / Q000378:metabolism; D007422:Intestines / Q000166:cytology / Q000276:immunology*; D051379:Mice; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; D002241:Carbohydrates; C508609:IL10 protein, human; D016753:Interleukin-10