Follicular T helper cells in patients with cholestatic liver disease – a comparative study

Background and aims: Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are the most common cholestatic liver diseases. Autoimmunity is thought to be involved in the pathogenesis of both diseases, however, autoantibodies are more closely associated with PBC than PSC. The aim of our study was to analyze and to compare the T cell phenotypes in PBC and PSC patients, focusing on the characteristics of follicular T helper cells (Tfh cells, PD1⁺CXCR5⁺ cells of CD4⁺T-lymphocytes). Tfh cells enable B cell maturation and antibody formation and their imbalance has been shown to cause the emergence of autoantibodies in various autoimmune diseases.

Methods: In this cross sectional study, 18 patients with PBC and 20 patients with PSC who were treated at our Liver Unit between 2014 and 2015 were included in the study and compared to a group of 23 healthy donors. Flow cytometry analyses were performed on isolated Peripheral Blood Mononuclear Cells stained with fluorescence-marked antibodies.

Results: Patients with PBC displayed higher numbers of T-lymphocytes (CD3⁺CD19^– cells, p = 0.004) compared to the healthy donor cohort, whereby both the CD4⁺- as well as the CD8⁺- subset were increased (p = 0.028, p = 0.048). Moreover, Tfh-cells were present at higher frequencies in patients with PBC (p = 0.05), with a significantly increased level of activation as characterized by expression of CXCR3⁺ (p < 0.001) or Ox40⁺ (p < 0.001). Regarding the frequency of naive CD4⁺ lymphocytes (CCR7⁺CD45RO^– cells) PBC patients expressed lower frequencies. Central and effector memory cells were not affected by any differences. In addition, frequencies of gut homing lymphocytes expressing CCR9 were similar in all groups.

Conclusion: Total T cells numbers and follicular T helper cells are increased in patients with PBC and Tfh cells display a more activated phenotype compared to those of healthy donors. In contrast, patients with PSC showed none of those features. These results suggest a role for Tfh cells in the pathogenesis of PBC but not PSC, and offer an explanation for the different roles of autoantibodies in cholestatic liver diseases.