The effects of extracorporeal photochemotherapy on T cell activation and regulatory mechanisms in patients with systemic sclerosis

In the study, we investigated the influence of extracorporeal photochemotherapy (ECP) on lymphocyte activation and cell death by determining CD95, Annexin V, CD69 and human leukocyte antigen (HLA)-DR expression on circulating T and B cells in systemic sclerosis (SSc) patients and assessed their changes after ECP therapies. Moreover, we evaluated the relationship between lymphocyte activation and the observed changes in immunoregulatory functions following ECP treatments. We enrolled 19 SSc patients, who received 12 ECP treatments in total. Blood samples were taken prior to the first therapy and 6 weeks after each cycle. Samples were also obtained from 16 healthy controls. Lymphocyte subgroups were quantified by flow cytometry. Initially, patients had higher numbers and percentages of peripheral CD95⁺ T cells, but not CD95⁺ B cells, compared to control values. After ECP treatments, values of CD95⁺ T cells decreased and became similar to controls. Annexin V expression on T and B cells did not change during the therapy. We observed a significant negative correlation between the changes in percentages of peripheral CD95⁺ T cells and CD4⁺CD25⁺ Treg cells. Although neither early-activated (CD69⁺) nor late-activated (HLA-DR+) T lymphocytes showed significant changes after ECP, clear negative correlations developed between them and the functional ability of CD4⁺CD25⁺ Treg cells after the last treatment. Our results indicate that the initial increase of CD95⁺ expression in SSc presumably reflects a physiological response to the pronounced autoimmune processes, which can be effectively attenuated by the restoration of regulative T cell numbers and functions as the result of ECP therapy.