茴香霉素对小鼠T细胞反应性及其杀伤作用的影响

Effects of Anisomycin on the reactivity and cytotoxicity of T lymphocytes in mice

目的茴香霉素对小鼠T细胞活化、反应性、杀伤作用及其同种异基因皮肤移植的影响。方法利用荧光标记的单克隆抗体双染技术结合流式细胞仪检测茴香霉素对小鼠CD3+T细胞早期及中期活化标志分子CD69和CD25表达的影响;用MTT法检测茴香霉素刺激下T细胞在单向或双向混合淋巴细胞反应中T细胞的反应性及其对大鼠肝癌(7919)细胞的杀伤效应;建立小鼠同种异基因皮肤移植动物模型,观察茴香霉素对移植皮肤存活时间的影响。结果在最佳剂量10.0ng/mL时,茴香霉素能够明显抑制T细胞表面分子CD69和CD25的表达,且能抑制单向或双向混合淋巴细胞反应中T细胞的反应性(P<0.01);10.0ng/mL茴香霉素亦能明显抑制T细胞对大鼠肝癌细胞的杀伤效应(P<0.01);5.0和15.0mg/kg茴香霉素能够明显延长小鼠移植皮肤的存活时间(P<0.01)。结论茴香霉素对T细胞的活化、反应性、杀伤效应及同种异基因皮肤移植排斥反应均有明显抑制作用,可能为治疗免疫反应性疾病提供新的策略。

Objective To investigate the effects of Anisomycin on the activity, reactivity, and cytotoxicity of T lymphocytesand theal- logenetic skin transplantation in mice. Methods The expression levels of CD69 and CIY25 on activated T cells was evaluated by fluorescinconjugated monoclonal antibody double labeling technique. The reactivity of T cells in unilateral or bilateral mixed lymphocyte reaction and the cytotoxicity the T cells against rat hver cancer cell hnes （7919） were detected by MTT assay. The mouse model of allogenetic skin transplantation was established to observe the effects of anlsomycin on survival time of skin transplantation. Results At the optimal dose of 10.0 ng/mL, Anisomycin could down-regulate the expression levels of CD69 and CD25 on T cell surface （ P 〈 0.01）, and could inhibit the reactivity of T cells in both unilateral and bilateral mixed lymphocyte reactions. At the same dose, Anisomycin could inhibit the cytotoxicity of T lymphocytes to 7919 cells, but there was no cytotoxicity of Anisomycin on 7919 cells. In vivo, both 5.0 mg/kg and 15.0 mg/kg Anisomycin could prolong the survival time of skin transplantation（ P 〈 0.01 ）. Conclusion The results suggest that Anisomycin definitely prohibits the activation, reactivity, and cytotoxicity of T lymphocytes and can inhibit the rejection of allogenetic skin transplantation in mice, which may offer a new strategy for the treatment of immunological diseases.