OX40对溃疡性结肠炎CD4+T细胞分泌细胞因子功能的影响

摘要

Objective To investigate the expression of OX40 on CD4+T cells in patients with ulcerative colitis (UC)and the role of OX40/OX40L interaction for the cytokine production of lamina propria(LP)-CD4+T cells from UC.Methotis LP-CD4+T cells were purified.The expression of OX40 molecule was measured with FACS.LP-CD4+T cells were cultured with different stimuli and proliferation was assessed.The cytokines concentrations of the culture supernatant were detected.Results No difference of the OX40 expression was observed among the CD4+T cells from peripheral blood(PB)of UC patients,LP of non-inflammatory colonic tissue in UC patients and control PB.However.the expression of OX40 was significantly higher on LP-CD4+T cells from inflammatory colonic tissue in UC patients.In vitro culture with antigen presenting cells,the levels of IFNγ and TNFα secreted by LP-CD4+T cells from the inflammatory colonic tissue were significantly higher than those from the non-inflammatory colonic tissue(both P＜0.01).The levels of IFNγ and TNFα secreted by LP-CD4+T cells from the inflammatory colonic tissue were further increased by anti-OX40 MoAb stimulation.but suppressed significantly by adding anti-OX40L MoAb (compared with non stimulation,P＜0.01,respectively).The IFNγ and TNFα secretion of the LP-CD4+T cells from the non-inflammatory colonic tissue were not significantly different with and without anti-OX40 or anti-OX40L MoAbs stimulation.IL-4 and IL-10 produced by LP-CD4+T cells from the inflammatory or non-inflammatory colonic tissue were not significantly changed when adding different stimuli.Conclusions OX40 is highly expressed on LP-CD4+T cells from inflammatory colonic tissue in patients with UC.AntiOX40L MoAb can inhibit the proinflammatory cytokines secreted by these cells.It is indicated that OX40+T cells are involved in the immunopathological process in UC and blockage of the interaction of OX40 and OX40Lis a new strategy to be considered for the treatment of the disease.%目的 研究溃疡性结肠炎(UC)CD4+T细胞表达OX40分子的差异及OX40对CD4+T细胞分泌细胞因子功能的影响.方法 用流式细胞仪测定OX40在不同来源的CD4+T细胞上的表达.用ELISA法测定CD4+T细胞分泌IFNγ、TNFα、IL-4和IL-10的水平.结果 UC病变部位黏膜固有层(LP)的CD4+T细胞表达OX40分子明显高于患者外周血和非病变部位LP-CD4+T细胞(P＜0.01).在体外与抗原呈递细胞(APC)共同培养,病变部位LP-CD4+T细胞分泌IFNγ和TNFα的水平明显高于非病变部位(P值均＜0.01).加入OX40单抗后,病变部位LP-CD4+T细胞分泌IFNγ和TNFα进一步增加(P值均＜0.01).相反,加入OX40配体(OX40L)单抗后病变部位LP-CD4+T细胞分泌IFNγ和TNFα的水平被明显抑制(P值均＜0.01).但OX40或OX40L单抗对非病变部位LP-CD4+T细胞分泌IFNγ、TNFα则无明显影响.另外,UC病变和非病变部位LP-CD4+T细胞分泌IL-4和IL-10的水平无明显的差别.结论 UC肠道病变部位LP-CD4+T细胞表达OX40明显增高.OX40L单抗能抑制病变部位LP-CD4+T细胞分泌促炎性细胞因子.阻断OX40/OX40L的作用可能为UC治疗提供一条新途径.