Release from regulatory T cell-mediated suppression during the onset of tissue-specific autoimmunity is associated with elevated IL-21.
The activity of regulatory T cells (Treg) is widely accepted to play a central role in preventing pathogenic immune responses against self-Ags. However, it is not clear why such regulation breaks down during the onset of autoimmunity. We have studied self-Ag-specific Treg during the induction of spontaneous diabetes. Our data reveal a shift in the balance between regulatory and pathogenic islet-reactive T cells in the pancreas-draining lymph nodes during disease onset. Treg function was not compromised during disease initiation, but instead conventional T cells showed reduced susceptibility to Treg-mediated suppression. Release from Treg suppression was associated with elevated levels of IL-21 in vivo, and provision of this cytokine abrogated Treg suppression in vitro and in vivo. These data suggest that immunological protection of a peripheral tissue by Treg can be subverted by IL-21, suggesting new strategies for intervention in autoimmunity.
Clough
Louise E
LE
Medical Research Council Center for Immune Regulation, University of Birmingham Medical School, Birmingham, UK.
Wang
Chun Jing
CJ
Schmidt
Emily M
EM
Booth
George
G
Hou
Tie Zheng
TZ
Ryan
Gemma A
GA
Walker
Lucy S K
LS
D019264:Adoptive Transfer; D000818:Animals; D015551:Autoimmunity; D001786:Blood Glucose / Q000032:analysis; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D018450:Disease Progression; D007108:Immune Tolerance; D007378:Interleukins / Q000276:immunology / Q000378:metabolism*; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D010179:Pancreas / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D000098546:Interleukin-21
D001786:Blood Glucose; D007378:Interleukins; D010047:Ovalbumin; D000098546:Interleukin-21