Meng Qianli, Yang Peizeng, Li Bing, Zhou Hongyan, Huang Xiangkun, Zhu Lianxiang, Ren Yalin, Kijlstra Aize
Zhongshan Ophthalmic Center, Uveitis Study Center, Sun Yat-sen University, Key Laboratory of Ophthalmology, Ministry of Education, Guangzhou, People's Republic of China.
Invest Ophthalmol Vis Sci. 2006 Oct;47(10):4444-52. doi: 10.1167/iovs.06-0201.
To study the expression and functional characteristics of programmed death-1 (PD-1) and its ligands in the spleens of mice undergoing anterior chamber-associated immune deviation (ACAID).
ACAID was induced in BALB/c mice by intracameral injection of ovalbumin (OVA). The expression of PD-1 and its ligands in the spleens of ACAID mice was determined by quantitative real-time PCR, Western blotting, and flow cytometry. In vitro proliferation assays, enzyme-linked immunosorbent assays, and adoptive transfer assays were used to investigate the functional characteristics of splenic CD4+PD-1+ T cells of ACAID mice.
Both mRNA and protein of PD-1, PD-L1, and PD-L2 were markedly upregulated in the spleens of ACAID mice compared with controls. CD4+PD-1+ T cells from ACAID mice produced large amounts of IL-10 and exhibited in vitro antigen-specific suppressive activity. CD4+PD-1+ T cells from ACAID mice were able to significantly inhibit the antigen-specific, delayed-type hypersensitivity response when adoptively transferred to naive mice.
CD4+PD-1+ T cells from ACAID mice, as regulatory cells, are involved in the induction of antigen-specific suppression in association with enhanced expression of IL-10. CD4+PD-1+ T cells in the murine spleen may represent a substantial population of regulatory T cells possibly responsible for the induction of ACAID after intracameral injection of antigen.
研究程序性死亡因子1(PD-1)及其配体在前房相关免疫偏离(ACAID)小鼠脾脏中的表达及功能特性。
通过向BALB/c小鼠前房内注射卵清蛋白(OVA)诱导ACAID。采用定量实时聚合酶链反应、蛋白质免疫印迹法及流式细胞术检测ACAID小鼠脾脏中PD-1及其配体的表达。运用体外增殖试验、酶联免疫吸附试验及过继转移试验研究ACAID小鼠脾脏CD4⁺PD-1⁺ T细胞的功能特性。
与对照组相比,ACAID小鼠脾脏中PD-1、PD-L1及PD-L2的mRNA和蛋白表达均显著上调。ACAID小鼠的CD4⁺PD-1⁺ T细胞产生大量白细胞介素-10,并表现出体外抗原特异性抑制活性。将ACAID小鼠的CD4⁺PD-1⁺ T细胞过继转移至未致敏小鼠后,能够显著抑制抗原特异性迟发型超敏反应。
ACAID小鼠的CD4⁺PD-1⁺ T细胞作为调节性细胞,与白细胞介素-10表达增强相关,参与抗原特异性抑制的诱导过程。小鼠脾脏中的CD4⁺PD-1⁺ T细胞可能代表了大量调节性T细胞群体,可能在眼内注射抗原后诱导ACAID的发生。