Altered Expression of Costimulatory Molecules in Behcet's Disease According to Clinical Activity

BACKGROUND: Behcet's Disease disease (BD) is a multisystemic inflammatory disorder. Several reports have suggested that autoimmunity, more precisely, failure to control autoreactive immune cells in the periphery may play a crucial role in BD. To produce a balanced immune response, key inhibitory costimulartory molecules that critically affect peripheral T cell tolerance and T cell function includes the cytotoxic T-lymphocyte antigen-4 (CTLA-4)/CD80, CD86 and programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) receptor/ligand systems are important. Also, regulatory T (Treg) cells play an important role in maintaining immune homeostasis. PURPOSE: The objective of the present study was to determine the immunopathological implication of costimulatory molecules in BD. I investigated cell surface expression of CTLA-4 and PD-1 on T cells and Treg cells, as well as cell surface expression of CD80, CD86, PD-L1 on antigen presenting cells (APCs). Also, I measured the concentration of soluble CTLA-4 (sCTLA-4) from serum and culture supernatants. MATERIALS AND METHODS: From January 2009 to June 2009, a total of 19 patients with BD were enrolled in this study. The disease control and healthy control (HC) group consisted of age- and sex-matched 8 recurrent aphthous ulcer (RAU) patients without any other evident disease and 10 healthy volunteers, respectively. PBMCs of subjects were cultured and stained with the appropriate fluorescent antibody for analysis by flow cytometry. To measure the sCTLA-4 concentrations in serum and in culture supernatants, ELISA was performed. To investigate the mRNA expression level of sCTLA-4 and PD-L1 in PBMCs, real time PCR was performed. RESULTS: In active BD group, the surface expression of CTLA-4 on CD4+ T cells was decreased in the stimulated state compared with HC group. In contrast, the surface expression of PD-1 on CD4+ T cells and CTLA-4 on CD8+ T cells did not show significant differences among each group. There were no differences of CD80 expression on APCs among each group, however, the surface expression of CD86 on APCs was impaired in active BD group compared with HC and inactive BD group in unstimulated state. Also, the surface expression of PD-L1 on APCs was decreased in active BD group compared with other group in unstimulated state. In addition, the surface expression of PD-L1 on APCs was decreased not only in active BD group, but also in inactive BD group at 48 hours after stimulation compared with other group. Proportion of CD4+CD25+highFOXP3+ T cells on CD4+ T cells was decreased in active BD group compared with inactive BD group. Significantly decreased percentage of CTLA-4 expressing CD4+CD25+high T cells was observed in active BD group compared with HC group in stimulated state, but surface PD-1 expression on CD4+CD25+high T cells did not show any differences among each group. Abnormal high serum concentration of sCTLA-4 was appeared in active BD group compared with HC group and RAU group. However, after stimulation, significant differences of sCTLA-4 concentration were not observed in culture supernatants. In accordance with these results, up-regulated expression of sCTLA-4 mRNA and decreased expression of PD-L1 mRNA in the active BD group were demonstrated compared with the HC group, although it was not statistically significant. CONCLUSION: This study shows importance of costimulatory molecules as regulator of balanced immune response in BD. From these results, I suggest that the abnormal expression of costimulatory molecules and serum concentration of sCTLA may have an implication in the pathogenesis of BD.

Author dc:creator

• 심, 지현

Contributors dc:contributor

• 이, 은소
• 박, 선
• 손, 성향
• 대학원 의학과
• 200824366

• Behcet's Disease
• CTLA-4
• sCTLA-4
• PD-L1

Language dc:language

en

Identifier

http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000010486
000000010486

OAI identifier oai:identifier

oai:repository.ajou.ac.kr:201003/1321