OX40在溃疡性结肠炎中的表达及意义

目的：研究溃疡性结肠炎（UC）患者OX40分子的表达,以及CD4＋OX40＋T细胞的免疫表型和免疫学功能.方法：从活动性UC患者肠粘膜标本中分离和纯化粘膜固有层CD4＋T细胞（LP-CD4＋T）.用FACS多参数分析法测定OX40在不同的CD4＋T细胞上的表达.用ELISA BrdU（5-溴脱氧尿嘧啶）法测定LP-CD4＋T细胞的增生程度以及不同刺激剂对它们增生程度的影响.结果：UC病变部位LP-CD4＋T细胞表达OX40明显高于健康对照者外周血、UC患者外周血CD4＋T细胞以及UC患者非病变部位CD4＋T的表达.LP-CD4＋OX40＋T细胞表达淋巴细胞活化标记CD25、CD38、CD45RO和HLA-DR均明显高于LP-CD4＋OX40-T细胞的表达（P＜0.01）.抗OX40单抗可明显增强病变部位LP-CD4＋T细胞的增生反应.相反,抗OX40L单抗则能明显抑制病变部位LP-CD4＋T细胞的增生.结论：OX40在UC患者病变部位的LP-CD4＋T细胞上表达明显增加,LP-CD4＋OX40＋T细胞是一类在原位被特异性抗原激活后扩增的T细胞,它们在UC的免疫病理机制中起重要作用.抗OX40L能够抑制其增生反应,可能是一种有效治疗UC的新方法.

The expression of OX40 in patients with ulcerative colitis

Objective:To investigate the expression of OX40 on CD4+T cells in the patients with ulcerative colitis(UC),and analyze the phenotype and functional features of lamina propria(LP)-CD4+OX40+T cells from UC.Methods:The expression of OX40 molecule was measured by FACS.LP-CD4+T cells were cultured with different stimuli,and proliferation was assessed by ELISA BrdU.Results:The expression of OX40 was significantly higher on LP-CD4+T cells from inflammatory colons in UC patients.LP-CD4+OX40+T cells expressed high levels of lymphocyte activation markers CD25,CD38,CD45RO and HLA-DR,which significantly higher than LP-CD4-T cells did respectively(all P<0.01).In vitro culture,APC induced proliferation response was further increased by anti-OX40 MoAb stimulation.But this proliferation response could be inhibited markedly by anti-OX40L MoAb.Conclusion:OX40 is highly expressed on LP-CD4+T cells from inflammatory colons in patients with UC.LP-CD4+OX40+T cells are a subset of autoreactive T cells stimulated by specific antigen in situ.Anti-OX40L MoAb can inhibit the proliferation response of this T cells.These data indicate that OX40+T cells are involved in the immunopathological process in UC,and targeting OX40 is a new considerable strategy for the treatment of this disease.