Analysis of circulating CD4+ and CD8+ T memory subsets in active type I autoimmune hepatitis and during its biochemical remission

FERREYRA SOLARI NE; BILLORDO LUIS ARIEL; BAZ PLÁCIDA; CHERÑAVSKY ALEJANDRA C

Berlín

Encuentro; 46th. Annual Meeting of the European Association for the Study of the Liver; 2011

European Association for the Study of the Liver

In type I autoimmune hepatitis (AIH-I), the chronically inflamed liver is characterized by the accumulation of memory T cells, driven by chemokines and cytokine receptors (R).The facets of CCR7 subsets of CD4+ or CD8+ memory T cells, i.e. central (LTCMCCR7-) and effector (LTEMCCR7+), depend upon T cells invested with distinct homing and effector capacities. We demonstrated that its biochemical remission was associated with a partial reversal of a deregulated immune response. Our aim was to evaluate CCR5, IL-18Rá and IL-12Râ1 expression in circulating memory T cell subsets during active AIH-I and biochemical remission on imunosupression. Methods Six patients with definite active AIH-I [37y (21-50)]; 9 patients during remission (AIH-IR) [47y (20-69), median follow up time: 2.5y (1-5)]and 9 age-matched healthy subjects as controls (Co) were included. Peripheral blood mononuclear cells (PBMC) were obtained by Ficoll-Hypaque gradients. Negatively selected CD45RO cells were isolated and analyzed by three-color flow-cytometry using PE-conjugated anti-CCR5, -IL18Rá and -IL-12Râ1; PerCP-conjugated anti-CD4 and -CD8; and FITC-conjugated anti-CCR7. Statistical analyses were performed using Kruskal-Wallis and Mann-Whitney U tests. ResultsAIH-I and AIH-IR CD4+LTEM subsets are increased (p=0.005, p=0.02 vs. Co) and reciprocally, CD4+LTCM subsets are decreased (p=0.004, p=0.02 vs. Co). Besides, both AIH-I and AIH-IR patients showed an increased expression of CCR5 (p=0.004, p=0.040 vs.Co) and IL-18Rá (p=0.002,p=0.050 vs. Co) on CD4+LTME subpopulations. The CD4+LTCM subpopulation is characterized by an increased expression of IL-18Rá in AIH-I compared with both AIH-IR and Co (p=0.050 and p=0.004). IL-12Râ1 expression within CD4+LT subsets does not differ between groups. Neither the extent of CD8+LTEM and CD8+LTCM subsets, nor the expression of CCR5, IL-18Rá and IL-12Râ1 differed among AIH-I, AIH-R and Co.ConclusionsPeripheral CD4+T memory subsets remain imbalanced despite the biochemical remission of AIH-I. However, immunosuppressive treatment is capable to reverse the phenotypic alterations observed in the CD4+LTCM. Since memory effectors achieve a fully mature phenotype after being recruited into the inflamed liver, the persistence of CCR5 and IL18Rá expression among CD4+LTEM may explain the partially reversed local immune response previously described. The distribution and phenotype of peripheral CD8+ T memory subsets remain unaffected in AIH-I.