Expression and Function of Inducible Costimulator on Peripheral Blood CD4+ T Cells in Patients With Ocular Behcet’s Disease

Abstract

Purpose: : To investigate the role of inducible costimulator (ICOS), an important costimulatory molecule in T cell activation in the pathogenesis of ocular Behcet’s disease (BD), we assessed its expression on peripheral blood CD4+ T cells and functional roles in patients with ocular BD.

Methods: : Seventeen patients with active BD, 18 with inactive BD, and 21 healthy individuals were enrolled in this study. We performed oligonucleotide microarray analysis using peripheral blood mononuclear cells from patients with ocular BD. Expression of ICOS on peripheral blood CD4+ T cells from patients with ocular BD and healthy volunteers were determined by flow cytometry. The functional costimulatory effect of ICOS on peripheral blood mononuclear cells were assessed by cytokine production.

Results: : Expression intensity of ICOS gene in PBMCs without stimulation was predominantly high in BD patients, which was further increased with stimulation. ICOS expression on freshly isolated CD4+ T cells from active BD patients was significantly upregulated compared with inactive BD patients and healthy individuals. Upon activation by Con A for 12 h, ICOS expression on CD4+ T cells was significantly higher in active BD and inactive BD patients compared to healthy individuals. In the absence of ConA, ICOS expression on CD4+ T cells was significantly higher in active BD compared to inactive BD and healthy individuals. The blockade of ICOS/B7RP-1 interaction by anti ICOS mAb significantly decreased IFN-γ production in patients with ocular BD.

Conclusions: : High ICOS expression on CD4+ T cells in ocular BD contributed to the upregulation of IFN-γ production, which indicated that the abnormality of ICOS costimulation may play an immunopathological role in the pathogenesis of ocular BD.

Keywords: uveitis-clinical/animal model • inflammation • immunomodulation/immunoregulation