Glycoantigens Induce Human Peripheral Tr1 Cell Differentiation with Gut-homing Specialization

Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
Journal of Biological Chemistry (Impact Factor: 4.57). 03/2011; 286(11):8810-8. DOI: 10.1074/jbc.M110.206011
Source: PubMed


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).

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