Article Text


P28 Defective T-regulatory function in autoimmune hepatitis may partially derive from a pro-inflammatory skewing of Gal9+T-regs
  1. R Liberal,
  2. G Mieli-Vergani,
  3. D Vergani,
  4. M S Longhi
  1. King's College London School of Medicine


Introduction In autoimmune hepatitis (AIH) CD4+CD25+ regulatory T-cells (T-regs) are defective in their ability to control CD4 T-cell effector function. T-regs express Galectin9 (Gal9), a β-galactosidase-binding-protein that inhibits Th1-mediated immune-responses by binding the T-cell-immunoglobulin-and-mucin-domain3 (Tim-3) on CD4 effector cells. In AIH T-regs express reduced levels of Gal9.

Aim To characterise lineage-specific transcription factor and cytokine profiles of peripheral-blood-derived Gal9+ T-regs in AIH.

Method 34 ANA/SMA+ patients (24 females; median age: 14.6 years) and 17 healthy subjects (HS, 12 females, median age: 29 years) were studied. The phenotype of circulating T-regs was determined by cytofluorimetry using CD4, CD25 and CD127 monoclonal antibodies. The frequency of cells positive for Gal9, FOXP3, T-bet, GATA3 and RORC and that of cells producing IFNγ, IL-10, TGF-β and IL-17 were determined by intracellular staining. T-reg suppressor function was evaluated in a proliferation assay following co-culture with CD25-Tim-3+ and CD25-Tim-3 autologous target cells.

Results Within Gal9+ cells the frequency of: (1) FOXP3+ cells was lower in AIH than in HS (14.4±2 vs 42.8±3.1, p<0.001); (2) T-bet+, GATA3+ and RORC+ cells was similar in AIH and HS; (3) IL-10-producing cells was lower in AIH than in HS (5.1±0.6 vs 9.1±0.5, p<0.001) but higher than in the Gal9 T-reg fraction for both (AIH: 5.1±0.6 vs 2.3±0.2, p=0.001; HS: 9.1±0.5 vs 3.3±0.4, p<0.001); (4) TGF-β-producing cells was lower in AIH than in HS (6.4±0.7 vs 8.1±0.4, p=0.04); (5) IFNγ- and IL-17-producing cells was higher in AIH than in HS (IFNγ: 4.4±0.6 vs 2.1±0.3, p=0.002; IL-17: 4.1±0.6 vs 1.8±0.2, p=0.002). Treatment with anti-IL-10 neutralising antibodies reduced T-reg ability to suppress CD25-Tim-3+ cell proliferation (AIH: 42% inhibition in the absence of antibodies vs 36% in their presence, p=0.06; HS: 56% vs 48%, p=0.04), while did not affect CD25Tim-3 cell proliferation.

Conclusion A skewing towards a pro-inflammatory phenotype and a reduced proportion of FOXP3+ and IL-10-producing cells within Gal9+ T-regs may contribute to defective immunoregulation in AIH. The reduction of Gal9+T-reg suppression following anti-IL-10 blockade both in health and AIH, suggests a role for IL-10 in Gal9+T-cell immune-regulatory function.

Statistics from

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.