Regulatory T Cell in drug-induced severe cutaneous adverse reactions (SCARs) during acute and recovery phase

Abstract

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a type of SCARs induced by various drugs. The autoimmune consequences were observed throughout the recovery phase ranging between 10 – 20 % of DRESS patients. The dynamics of regulatory T cells (Tregs) are thought to be responsible for the many symptoms of DRESS. They may be a key player in developing autoimmune sequelae in this syndrome. This study concentrated on the number and function of CD4+CD25+CD127-FoxP3+ Tregs in autoimmune development in DRESS patients. CD4+CD25+CD127-FoxP3+ Tregs and their immunophenotyping were characterized using peripheral blood mononuclear cells (PBMCs) from patients by Flow cytometry techniques. The suppressive function of Tregs was determined using suppression assay by co-culture between autologous Treg and effector T cells. NanoString technology was used to study mRNA profiles to explore genes associated with Tregs. CD4+CD25+CD127-FoxP3+ Tregs in DRESS with autoimmune sequelae at the acute phase tended to be lower than DRESS without autoimmune sequelae, SJS/TEN patients, and in healthy controls. The immunophenotyping showed that the expression of CTLA-4, LAG-3, GITR, and IL-10 were higher in DRESS with autoimmune sequelae patients. However, the suppression of Treg on Teff proliferation was also lower in DRESS with autoimmune sequelae patients. The mRNA profile showed downregulation of genes associated with Treg function since the acute phase of DRESS with autoimmune sequelae. In conclusion, this study illustrated the regulatory functions of Tregs were altered since the acute phase after the onset of DRESS, which might be used as prognostic factors for long-term complications in DRESS subjects.