CD4+ T cell tolerance to tissue-restricted self antigens is mediated by antigen-specific regulatory T cells rather than deletion Journal Article
| Authors: | Legoux, F. P.; Lim, J. B.; Cauley, A. W.; Dikiy, S.; Ertelt, J.; Mariani, T. J.; Sparwasser, T.; Way, S. S.; Moon, J. J. |
| Article Title: | CD4+ T cell tolerance to tissue-restricted self antigens is mediated by antigen-specific regulatory T cells rather than deletion |
| Abstract: | Deletion of self-antigen-specific T cells during thymic development provides protection from autoimmunity. However, it is unclear how efficiently this occurs for tissue-restricted self antigens, or how immune tolerance is maintained for self-antigen-specific T cells that routinely escape deletion. Here we show that endogenous CD4+ T cells with specificity for a set of tissue-restricted self antigens were not deleted at all. For pancreatic self antigen, this resulted in an absence of steady-state tolerance, while for the lung and intestine, tolerance was maintained by the enhanced presence of thymically-derived antigen-specific Foxp3+ regulatory T (Treg) cells. Unlike deletional tolerance, Treg cell-mediated tolerance was broken by successive antigen challenges. These findings reveal that for some tissue-restricted self antigens, tolerance relies entirely on nondeletional mechanisms that are less durable than T cell deletion. This might explain why autoimmunity is often tissue-specific, and it offers a rationale for cancer vaccine strategies targeting tissue-restricted tumor antigens. © 2015 Elsevier Inc. |
| Keywords: | controlled study; promoter region; nonhuman; transcription factor foxp3; antigen expression; cell proliferation; mouse; animal tissue; steady state; animal experiment; in vivo study; immunological tolerance; regulatory t lymphocyte; antigen presentation; antigen specificity; messenger rna; antigen recognition; cd4+ t lymphocyte; cytokine production; autoimmunity; interleukin 17; cell expansion; t lymphocyte subpopulation; helper cell; tissue specificity; t lymphocyte antigen; lung parenchyma; chemokine receptor cxcr5; priority journal; article; intestinal tissue |
| Journal Title: | Immunity |
| Volume: | 43 |
| Issue: | 5 |
| ISSN: | 1074-7613 |
| Publisher: | Cell Press |
| Date Published: | 2015-11-17 |
| Start Page: | 896 |
| End Page: | 908 |
| Language: | English |
| DOI: | 10.1016/j.immuni.2015.10.011 |
| PROVIDER: | scopus |
| PMCID: | PMC4654997 |
| PUBMED: | 26572061 |
| DOI/URL: | |
| Notes: | Export Date: 2 December 2015 -- Source: Scopus |
