1). The granzyme B MFI correlated with the ALT levels (r2 = 0.16, P = 0.047). Granzyme B expression, considered as both the percentage of positive cells and the MFI, correlated with the bilirubin levels (Fig. 2). The number of Vδ1-positive cells producing IFN-γ after stimulation with PMA and ionomycin was higher in AIH patients versus HCs (3.69% ± 0.66% versus 1.76% ± 0.36%, P = 0.02), with no difference between [A] patients and [R] patients. IFN-γ MFI levels and production by the Vδ2 subset were comparable in all groups. No correlations were found between CX5461 IFN-γ

production and laboratory indices. The stimulation of PBMCs with α-GalCer resulted in a higher expansion of CD3+CD56+ cells with respect to the baseline in patients (567% ± 153%) versus

HCs (190% ± 25%), the poststimulation NKT cell frequency being similar in the two groups (25.0% ± 6.2% in HCs versus 19.8% ± 11.2% in AIH patients, P = 0.51). Although no difference in the frequency of IFN-γ–producing NKT cells was noted between the two groups, the frequency of IL-4–producing NKT cells was lower in AIH patients versus HCs (Table 3), this decrease being particularly evident in AIH [A] patients (15.0% ± 2.5%, P = 0.035; Table 3). FOXP3+ cells were detected in the portal tracts of five of seven liver biopsy samples from tested AIH patients (all were histologically active, and two had normal aminotransferase levels; Fig. 3, Supporting Fig. 1, and Supporting Table 1). FOXP3+ cells represented a small proportion of the portal tract inflammatory infiltrate, their presence and number being unrelated to the liver disease 上海皓元 stage. After the addition of CD4+ CD25hi T lymphocytes, the mean

3-deazaneplanocin A concentration CD4+CD25− T cell count per minute decreased by 57% in HCs (from 27,150 ± 7172 to 12,948 ± 4697 cpm, P = 0.001) and by 34% in AIH patients (from 22,114 ± 3167 to 16,424 ± 3170 cpm, P = 0.02), with the inhibition percentage lower than that in HCs (P = 0.009). No significant difference was noted in the suppression ability of Tregs between AIH [A] patients and AIH [R] patients, the inhibition of CD4+CD25− T cell proliferation being 27% in the former and 37% in the latter. Control experiments in which CD4+CD25− T lymphocytes were used instead of Tregs had no detectable effect on the proliferation of CD4+ CD25− T cells in AIH patients or HCs. Liver damage in AIH is orchestrated by CD4+ T lymphocytes that recognize autoantigenic liver cell epitopes.35 If not effectively controlled by immunoregulation, these autoreactive T cells perpetuate self-aggression against the liver and lead to chronic hepatitis and cirrhosis.3 Compelling evidence obtained from animal models indicates that CD4+CD25hi lymphocytes prevent or cure autoimmune disorders by restoring immunotolerance to autoantigens.8, 9 Numerical and functional CD4+CD25hi cell impairment has been reported in a number of organ-specific autoimmune diseases, including diabetes,36 multiple sclerosis,37 rheumatoid arthritis,38 and primary biliary cirrhosis.