细胞毒性T淋巴细胞相关抗原-4融合蛋白对鼠单纯疱疹性角膜基质炎抑制作用的研究

Inhibition by CTLA-4Ig on herpetic stromal keratitis in a murine model

目的 研究细胞毒性T淋巴细胞相关抗原 4融合蛋白 (cytotoxicTlymphocyte associatedantigen 4immunoglobulin ,CTLA 4Ig)对鼠单纯疱疹性角膜基质炎 (herpeticstromalkeratitis ,HSK)的抑制作用。方法 用单纯疱疹病毒 1型 (herpessimplexvirustype 1,HSV 1)接种于BALB/c鼠角膜上建立HSK动物模型 ,采用CTLA 4Ig阻断B7:CD2 8/CTLA 4协同刺激途径 ,抑制T淋巴细胞增殖、分化为效应细胞 ;观察HSK的发病率、临床特征、角膜组织学改变、角膜病毒滴度、迟发型超敏反应及抗原刺激脾细胞分泌细胞因子的情况。结果 CTLA 4Ig可减少小鼠外周血中CD4+T淋巴细胞 ( 81 6 %)及CD8+T淋巴细胞 ( 6 7 9%) ,阻止鼠发生HSK、减轻角膜混浊程度及角膜内炎性细胞的浸润、损伤鼠的迟发型超敏反应能力 ,抑制鼠脾细胞分泌辅助性T淋巴细胞 1型 (T helper 1,Th1)细胞因子 ;但不影响角膜病毒滴度及小鼠死亡率。结论 用CTLA 4Ig阻断B7:CD2 8/CTLA 4协同刺激途径 ,能够抑制T淋巴细胞增殖并抑制CD4+Th1细胞的功能 ,阻止HSK发病 ,减轻HSK的严重程度。

Objective To investigate the inhibition by CTLA-4Ig on herpetic stromal keratitis (HSK). Methods BALB/c mice infected with HSV-1 Mckrae strain by corneal scarification were injected intraperitoneally with murine CTLA-4Ig given on days 0, +2, +4 after the infection. The effects of CTLA-4Ig on HSK were evaluated. Results As measured by flow cytometry, in the mice treated with CTLA-4Ig, 81.6% of CD4 +T cells and 67.9% of CD8 +T cells were reduced. CTLA-4Ig halted the onset of HSK, reduced the corneal stromal opacification of HSK, prevented extensive cellular infiltration in cornea, impaired the delayed type hypersensitivity and inhibited splenocytes producing Th1 cytokines. Conclusions The results provide evidence that blockade of B7:CD28/CTLA-4 costimulation by CTLA-4Ig can inhibit the proliferation of T cells and Th1 response and impair onset and severity of HSK.