Characterization of CD24⁺ T Cells and Their Cytokine Signature in Autoimmune Hepatitis

CD24, expressed by various immune cells, plays a crucial role in controlling the pathogenesis of autoimmune diseases including murine AIH, however, its role on human T cells in AIH is unclear. This study aimed to determine the percentage and cytokine profile of peripheral CD24⁺ T cells in AIH and establish their correlation with disease severity and fibrosis, along with CD24 expression in liver biopsy specimens.

Eighteen patients with AIH, fulfilling the Simplified Scoring Criteria and 20 healthy controls (HC) were included in the study. The percentage of CD24⁺ T cells and their cytokine profile were analyzed by flow cytometry. CD24 immunohistochemistry was performed on liver biopsies. The modified Ishak Knodell scoring system was used for assessing disease severity and fibrosis.

The mean age of patients was 34.83 ± 16.52 years. There were 11 females and 7 males. A higher percentage of CD4⁺CD24⁺ T cells (AIH: 1.4 ± 0.23 vs HC: 0.78 ± 0.07) were seen in AIH patients compared to HC. CD4⁺CD24⁺IFN-γ⁺ (AIH: 0.28 ± 0.08 vs HC: 0.09 ± 0.01) and CD8⁺CD24⁺IFN-γ⁺ T cells (AIH: 0.42 ± 0.1 vs HC: 0.15 ± 0.03) were also elevated in AIH compared to HC, with CD8⁺CD24⁺IFN-γ⁺ T cells correlated with the disease severity (r = 0.505). CD8⁺CD24⁺IL-4⁺ T cells were also higher (AIH: 0.62 ± 0.16 vs HC: 0.18 ± 0.03) in AIH patients. Additionally, we observed increased percentage of IL-4 producing CD4⁺ (AIH: 4.09 ± 0.76 vs HC: 2.0 ± 0.22) and CD8⁺ T (AIH: 5.9 ± 1.1 vs HC: 1.9 ± 0.22) cells in AIH compared to HC. Subgroup analysis between seropositive and seronegative AIH showed increased percentage of CD4⁺CD24⁺IL-17A⁺ T cells (Seropositive AIH: 0.17 ± 0.04 vs Seronegative AIH: 0.04 ± 0.01, P = 0.025).

This study suggests that CD24 may influence the production of IFN-γ and IL-4 which reflect the Th1 and Th2 responses respectively in AIH. Additionally, a Th17 dominant immune response in seropositive AIH highlights its role in antibody production. Further studies are needed to understand the immunological heterogeneity in AIH and its therapeutic implications.