J H Sim1, M J Park, S Park, E-S Lee. 1. Department of Dermatology, Ajou University School of Medicine, Suwon, Yeongtong-Gu, Suwon 443-721, Korea.
Abstract
BACKGROUND: The reduced expression of molecules limiting excessive immune responses has been considered a pathogenic mechanism associated with autoimmune diseases. OBJECTIVES: To understand the implications of costimulatory molecules in Behçet's disease (BD), the expression of CTLA-4 and PD-1 on T-cell subsets and of their ligands CD80, CD86 and PD-L1 on antigen-presenting cells (APCs) was investigated. METHODS: Peripheral blood mononuclear cells (PBMC) from 11 patients with active BD, eight patients with inactive BD, eight patients with recurrent aphthous ulcers and 10 healthy volunteers as healthy controls (HC) were stimulated with phorbol myristate acetate and ionomycin. The expression of costimulatory molecules was then analysed by flow cytometry. Soluble CTLA-4 (sCTLA-4) concentrations were determined by enzyme-linked immunosorbent assay and the transcript level of PD-L1 was measured by real-time polymerase chain reaction. The PD-L1 expression in skin lesions of patients with BD was evaluated by immunohistochemistry. RESULTS: Compared with the HC group, reduced expression of CTLA-4 in CD4+ T cells after stimulation was observed in the active BD group, with no difference in the production of sCTLA-4. CD86 expression, in the resting APCs, was reduced in the active BD group compared with the HC group. PD-L1 expression in the APCs was decreased in the active BD group with or without stimulation of cells. Concordantly, the mRNA levels of PD-L1 in PBMC, and PD-L1 expression in the cutaneous lesions, were low in the active BD group. CONCLUSIONS: The results of this study suggest that altered expression of PD-L1, CTLA-4 and CD86 may be involved in the pathogenesis of BD.
BACKGROUND: The reduced expression of molecules limiting excessive immune responses has been considered a pathogenic mechanism associated with autoimmune diseases. OBJECTIVES: To understand the implications of costimulatory molecules in Behçet's disease (BD), the expression of CTLA-4 and PD-1 on T-cell subsets and of their ligands CD80, CD86 and PD-L1 on antigen-presenting cells (APCs) was investigated. METHODS: Peripheral blood mononuclear cells (PBMC) from 11 patients with active BD, eight patients with inactive BD, eight patients with recurrent aphthous ulcers and 10 healthy volunteers as healthy controls (HC) were stimulated with phorbol myristate acetate and ionomycin. The expression of costimulatory molecules was then analysed by flow cytometry. Soluble CTLA-4 (sCTLA-4) concentrations were determined by enzyme-linked immunosorbent assay and the transcript level of PD-L1 was measured by real-time polymerase chain reaction. The PD-L1 expression in skin lesions of patients with BD was evaluated by immunohistochemistry. RESULTS: Compared with the HC group, reduced expression of CTLA-4 in CD4+ T cells after stimulation was observed in the active BD group, with no difference in the production of sCTLA-4. CD86 expression, in the resting APCs, was reduced in the active BD group compared with the HC group. PD-L1 expression in the APCs was decreased in the active BD group with or without stimulation of cells. Concordantly, the mRNA levels of PD-L1 in PBMC, and PD-L1 expression in the cutaneous lesions, were low in the active BD group. CONCLUSIONS: The results of this study suggest that altered expression of PD-L1, CTLA-4 and CD86 may be involved in the pathogenesis of BD.