PMO-137 Phenotypic and functional signature of CD4POSCD25HIGHCD127 low regulatory T-cells in autoimmune hepatitis. (28th May 2012)

• Record Type: Journal Article
• Authors: Liberal, R; Grant, C; Mieli-Vergani, G; Vergani, D; Longhi, M
• Is Part Of: Gut. Volume 61(2012)Supplement 2
• Page Start: A128
• Page End: A129
• Publication Date: 2012-05-28
• Subjects: Gastroenterology -- Periodicals; 616.33
• DOI: 10.1136/gutjnl-2012-302514b.137
• Languages: English
• ISSNs: 0017-5749

Abstract

Abstract : Introduction: In autoimmune hepatitis (AIH) CD4 pos CD25 high regulatory T-cells (T-regs), a subset central to immune-tolerance, are numerically defective and impaired in their ability to control effector cell function. At variance with CD4 effectors, T-regs, classically known as CD25 high and FOXP3 pos, express low levels of the activation marker CD127. The aim of the current study was to provide a phenotypic and functional profile of CD4 pos CD25 high CD127 low T-regs (CD127 low T-regs) in AIH and to explore to what extent absence or low levels of CD127 impact on T-reg ability to suppress. Methods: 20 ANA/SMA+ AIH patients and 12 healthy subjects (HS) were studied. T-reg phenotype was determined by flow cytometry using antibodies to CD4, CD25, CD127, CTLA-4 and Galectin-9, a molecule linked to T-reg ability to suppress. T-reg transcription factor and cytokine profile were assessed by intracellular staining. CD127 low T-reg ability to suppress was evaluated in a proliferation assay following co-culture with CD25 neg target cells. Results: In AIH CD4 pos CD25 high cells contained fewer CD127 low cells than in HS. Compared to conventional CD4 pos CD25 high (cT-regs), CD127 low T-regs from both AIH and HS had a) higher numbers of FOXP3 pos, CTLA-4 pos, Galectin-9 pos and IL-10 pos cells; b) lower numbers of T-bet pos, RORC pos, IFNg pos and IL-17 pos cells; and c) similar numbers of TGF-b pos cells. In AIH, CD127 low T-regs contained fewer FOXP3 pos, CTLA-4 pos, Galectin-9 pos, IL-10 pos and TGF-b pos cells and higher frequencies of T-bet pos, RORC pos, IFNg pos and IL-17 pos cells than in HS. CD127 low T-regs inhibited CD25 neg cell proliferation more effectively than cT-regs, though less markedly in AIH than in HS. In AIH, treatment with anti-IFNg and anti-IL-17 neutralising antibodies ameliorated the suppressive ability of cT-regs, while leaving unchanged that of CD127 low T-regs; exposure to anti-IL-10 neutralising antibodies reduced cT-reg suppression in HS, but not in AIH. Conclusion: CD127 low T-regs bear the phenotypic and functional signature of "true T-regs". Low numbers and reduced suppressive function of CD127 low T-regs in AIH may contribute to breakdown of immune-tolerance by permitting effector cells to perpetrate hepatocyte damage. Competing interests: None declared.