Frassanito M A, Dammacco R, Fusaro T, Cusmai A, Guerriero S, Sborgia C
Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine and Clinical Oncology, University of Bari Medical School, Bari, Italy.
Clin Exp Immunol. 2003 Aug;133(2):233-9. doi: 10.1046/j.1365-2249.2003.02214.x.
In this study, we assessed the Th1/Th2 polarization of the immune response and the involvement of dendritic cells (DC) and Th1 lymphocytes in the pathogenesis of uveitis. Thirty-seven patients with chronic idiopathic uveitis were enrolled: 21 of them had active uveitis and the remaining 16 were in complete remission. Patients with active uveitis were characterized as follows: 5 had intermediate uveitis, 5 panuveitis and the remaining 11 posterior uveitis. Thirteen healthy subjects were also studied as controls. Patients with active uveitis were treated with cyclosporin-A (CsA) associated to low doses of prednisone (PDS) and studied at baseline and after 6 months of therapy. Analysis of cytokine-producing CD3+ lymphocytes revealed a strong Th1 polarization of the immune response in patients with active uveitis. Th1 lymphocytes paralleled serum IL-12 levels and the response to therapy, which greatly reduced both IFN-gamma+/CD3+ lymphocytes and serum IL-12 levels, associated with a general clinical improvement. In vitro studies demonstrated that DC from untreated patients with active uveitis were mature and functionally active. In fact, they showed a higher ability to stimulate cell proliferation of allogeneic T cells in primary mixed lymphocyte reaction (MLR) and produced larger amounts of IL-12 than DC from CsA/PDS-treated patients and those in remission. These results demonstrate that CsA/PDS therapy impairs the capacity of mature DC to secrete IL-12 and inhibits their MLR activity.
在本研究中，我们评估了免疫反应的Th1/Th2极化以及树突状细胞（DC）和Th1淋巴细胞在葡萄膜炎发病机制中的作用。纳入了37例慢性特发性葡萄膜炎患者：其中21例患有活动性葡萄膜炎，其余16例处于完全缓解期。活动性葡萄膜炎患者的特征如下：5例为中间葡萄膜炎，5例为全葡萄膜炎，其余11例为后葡萄膜炎。还研究了13名健康受试者作为对照。活动性葡萄膜炎患者接受环孢素A（CsA）联合低剂量泼尼松（PDS）治疗，并在基线和治疗6个月后进行研究。对产生细胞因子的CD3+淋巴细胞的分析显示，活动性葡萄膜炎患者的免疫反应存在强烈的Th1极化。Th1淋巴细胞与血清IL-12水平及治疗反应平行，治疗使IFN-γ+/CD3+淋巴细胞和血清IL-12水平均大幅降低，同时临床总体改善。体外研究表明，未经治疗的活动性葡萄膜炎患者的DC成熟且功能活跃。事实上，与接受CsA/PDS治疗的患者及缓解期患者的DC相比，它们在原发性混合淋巴细胞反应（MLR）中刺激同种异体T细胞增殖的能力更强，且产生的IL-12量更多。这些结果表明，CsA/PDS治疗损害了成熟DC分泌IL-12的能力，并抑制了它们的MLR活性。
