Peripherally Induced Tolerance Depends on Peripheral Regulatory T Cells That Require Hopx To Inhibit Intrinsic IL-2 Expression
| Autor: | Adeleye Opejin, Jacob G. Henderson, Jonathan A. Epstein, Andrew Jones, Cindy Gross, Rajan Jain, Daniel Hawiger, Richard A. Flavell |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Interleukin 2
Encephalomyelitis T cell Immunology Inflammation Autoimmunity Biology medicine.disease_cause Autoantigens T-Lymphocytes Regulatory Article Immune tolerance Mice Antigen medicine Immune Tolerance Immunology and Allergy Animals Regulation of gene expression Homeodomain Proteins Mice Knockout Dendritic Cells medicine.disease Disease Models Animal medicine.anatomical_structure Gene Expression Regulation Interleukin-2 medicine.symptom medicine.drug |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 195(4) |
| ISSN: | 1550-6606 |
| Popis: | Dendritic cells (DCs) can induce peripheral immune tolerance that prevents autoimmune responses. Ag presentation by peripheral DCs under steady-state conditions leads to a conversion of some peripheral CD4+ T cells into regulatory T cells (Tregs) that require homeodomain-only protein (Hopx) to mediate T cell unresponsiveness. However, the roles of these peripheral Tregs (pTregs) in averting autoimmune responses, as well as immunological mechanisms of Hopx, remain unknown. We report that Hopx+ pTregs converted by DCs from Hopx− T cells are indispensible to sustain tolerance that prevents autoimmune responses directed at self-Ags during experimental acute encephalomyelitis. Our studies further reveal that Hopx inhibits intrinsic IL-2 expression in pTregs after antigenic rechallenge. In the absence of Hopx, increased levels of IL-2 lead to death and decreased numbers of pTregs. Therefore, formation of Hopx+ pTregs represents a crucial pathway of sustained tolerance induced by peripheral DCs, and the maintenance of such pTregs and tolerance requires functions of Hopx to block intrinsic IL-2 production in pTregs. |
| Databáze: | OpenAIRE |
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