Abstract
Purpose:
Behcet’s disease (BD) is a chronic, systemic and recurrent inflammatory disease with overreacted Th17/Th1 cell immune response. Recent studies have shown that B and T lymphocyte attenuator (BTLA) plays a regulatory role in the excessive immune and inflammatory response. In this study, we investigated whether BTLA activation could be exploited to inhibit the development of abnormal immune responses in BD patients.
Methods:
BTLA mRNA and protein expression in peripheral blood mononuclear cells (PBMCs) and CD4+ T cells from active ocular BD patients and normal controls was examined using RT-PCR and flow cytometry. The production of IL-17 and IFN-gamma by BTLA+CD4+ T cells and BTLA-CD4+ T cells were detected by flow cytometry. ELISA and flow cytometry were performed to study the effect of BTLA on Th17/Th1 cell response and DC function using agonistic anti-BTLA antibody.
Results:
The expression of BTLA was significantly decreased in active ocular BD patients as compared to normal controls. Decreased expression of BTLA was associated with increased Th17/Th1 cell immune response in ocular BD patients. Activation of BTLA inhibited the abnormal Th17/Th1 cell response and expression of IL-22 by CD4+ T cells both in patients and normal controls. Addition of the agonistic anti-BTLA antibody resulted in a decreased production of Th17/Th1 related cytokines IL-1β, IL-6, IL-23 and IL-12p70, and reduced expression of CD40 in DCs.
Conclusions:
Decreased expression of BTLA in the ocular BD patients may be not able to exert its negative regulation effect on Th17 and Th1 cell immune responses and DC function and therefore is involved in the development and recurrence of this disease. Agonistic agents of BTLA may be a potential therapeutic approach for BD and other inflammatory diseases mediated by Th17/Th1 immune responses.