Regulatory T-cell Activation Pathways in Patients With Chronic Graft-versus-host Disease Undergoing Extracorporeal...

Induction of immune tolerance by the activation of regulatory T (Tregs) cells after extracorporeal photopheresis (ECP) appears to influence the response to treatment in patients with chronic graft-versus-host disease (cGvHD). This study examined the activation mechanisms of Tregs and their potential link to the expression of FOXP3, TP53, and SELPLG genes. Results were compared with the therapeutic response to ECP.

The study included six patients with cGvHD who underwent at least four cycles of ECP. The samples were collected from peripheral blood (PB) and from apheresis material before and after ECP, which was then used to establish cell cultures. The percentage of Tregs and their subpopulations were assessed using multicolor flow cytometry. Gene expression levels were evaluated using quantitative PCR (qPCR).

A statistically significant increase in the expression levels of TP53 gene was found in the fourth ECP cycle in patients with partial response (PR) compared to patients with stable disease (SD). Patients with PR were characterized by higher mRNA levels for the TP53 and SELPLG genes after 48 h of culture. Patients with PR had a statistically significant higher percentage of Tregs including activated HLA-DR+ Tregs.

Patients with PR demonstrated elevated gene expression levels in 48-h mononuclear cell cultures, which correlated with their clinical response to treatment. They also had a higher baseline percentage of Tregs, which did not correlate with elevated FOXP3 or other gene expression levels.