CD4+Foxp3+ regulatory T cell expansion induced by antigen-driven interaction with intestinal epithelial cells independent of local dendritic cells
Background:Regulatory T cells (Tregs) have potential anti-inflammatory effects and are likely to be important in the pathogenesis of chronic inflammatory bowel disease (IBD). However, the induction and expansion of Tregs at sites of mucosal inflammation are not yet fully understood and may involve a...
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Published in | Gut Vol. 58; no. 2; pp. 211 - 219 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
BMJ Publishing Group Ltd and British Society of Gastroenterology
01.02.2009
BMJ Publishing Group BMJ Publishing Group LTD |
Subjects | |
Online Access | Get full text |
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Summary: | Background:Regulatory T cells (Tregs) have potential anti-inflammatory effects and are likely to be important in the pathogenesis of chronic inflammatory bowel disease (IBD). However, the induction and expansion of Tregs at sites of mucosal inflammation are not yet fully understood and may involve antigen presentation by local dendritic cells (DCs) and/or intestinal epithelial cells (IECs).Methods:To determine the unique ways in which the gut induces or expands Tregs, a transgenic mouse model that is based on the specific expression of a model autoantigen (influenza haemagglutinin (HA)) in the intestinal epithelium (VILLIN-HA) was used. Gut-associated DCs and IECs isolated from these mice were phenotypically and functionally characterised for the potential to interact with HA-specific Tregs in vitro and in vivo.Results:Intestinal self-antigen expression leads to peripheral expansion of antigen-specific CD4+Foxp3+ Tregs. Although gut-associated DCs can induce antigen-specific CD4+Foxp3+ T cell proliferation, in vivo depletion of DCs did not preclude proliferation of these cells. Interestingly, antigen presentation by primary IECs is sufficient to expand antigen-specific CD4+Foxp3+ Tregs efficiently. This is dependent on major histocompatibility complex class II, but, in contrast to DCs, is unlikely to require transforming growth factor β and retinoic acid.Conclusion:This study provides experimental evidence for a new concept in mucosal immunity: in contrast to current thinking, expansion of Tregs can be achieved independently of local DCs through antigen-specific IEC–T cell interactions. |
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Bibliography: | local:gutjnl;58/2/211 ArticleID:gt151720 Additional methods and figures are published online only at http://gut.bmj.com/content/vol58/issue2 href:gutjnl-58-211.pdf istex:8121F24A51F94DDA6A099C4B7FB8C9EBEFFEA56B ark:/67375/NVC-XTLWX1GW-V PMID:18832523 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0017-5749 1468-3288 |
DOI: | 10.1136/gut.2008.151720 |