Anti‐CD40 monoclonal antibody ameliorates experimental autoimmune uveoretinitis in mice. (3rd July 2020)

• Record Type: Journal Article
• Authors: Xu, Lei; Gao, Jie; Pan, Yongquan; Tian, Na; He, Mingzhong; Jin, Lei; Chen, Feilan
• Is Part Of: Veterinary ophthalmology. Volume 23:Number 5(2020)
• Page Start: 797
• Page End: 805
• Publication Date: 2020-07-03
• Subjects: CD40 -- dendritic cells -- experimental autoimmune uveoretinitis -- MHC class II molecules -- proliferation -- TNF‐α; Veterinary ophthalmology -- Periodicals; 636.08977
• DOI: 10.1111/vop.12799
• Languages: English
• ISSNs: 1463-5216

Abstract

Abstract: Objective: To investigate the effects of CD40 on ocular inflammation in experimental autoimmune uveoretinitis (EAU) in B10.RIII mice. Animals studied: EAU‐susceptible B10.RIII mice were subcutaneously immunized with interphotoreceptor retinoid‐binding protein (IRBP) 161‐180 in complete Freund's adjuvant and evaluated clinically and pathologically on days 7, 14, 21, 28, and 35 postimmunization. Anti‐CD40 antibody was intraperitoneally injected into mice every other day from days 7 to 14 postimmunization. Phosphate‐buffered saline (PBS)‐injected EAU mice were used as the controls. Procedures: The frequencies of CD11c + CD40 + dendritic cells (DCs), CD11c + MHC‐II + DCs, and CD11c + CD40 + MHC‐II + DCs in splenocytes were evaluated by flow cytometry on days 0, 7, 14, and 21 after immunization. Tumor necrosis factor (TNF)‐α and interleukin (IL)‐6 production in CD11c + DCs was assessed by ELISA. IRBP‐specific lymphocyte proliferation was assessed using a modified MTT cell proliferation assay. Results: The number of CD11c + CD40 + DCs, CD11c + MHC‐II + DCs, and CD11c + CD40 + MHC‐II + DCs increased at the onset of EAU, peaked at the height of disease severity, and was sustained at a high level until day 21. Treatment with anti‐CD40 antibody significantly alleviated clinical and pathological activities related to EAU. Compared with the control mice, antibody‐treated EAU mice showed few CD11c + CD40 + DC and CD11c + CD40 + MHC‐II + DC frequencies in splenocytes. The anti‐CD40 antibody significantly suppressed IRBP‐specific lymphocyte proliferation and TNF‐α and IL‐6 production by DCs in EAU mice. Conclusions: The increased expression of CD40 and major histocompatibility complex (MHC) class II molecules in the splenocytes of EAU mice were correlated with inflammatory activity. Anti‐CD40 treatment can significantly attenuate EAU activity by inhibiting systemic IRBP‐specific immune responses.