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粘附分子对CD3介导的胸腺细胞[Ca2+]i应答的影响

EFFECT OF LFA-1ON THE[Ca2+]i RESPONSE IN CD3-MEDIATED ACTIVATION OF THYMOCYTES

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【作者】 路力生陈慰峰

【Author】 LuLi-shengandChen Wei-feng(Department of lmmunology,Beijing Medical U niversity 100083)

【机构】 北京医科大学免疫学系

【摘要】 LFA-1和ICAM-1广泛表达于各胸腺细胞亚群,但ICAM-1在PNA ̄+细胞的表达下调。本文报道:用抗LFA-1/ICAM-1和抗CD3单抗,分析了粘附分子LFA-1/ICAM-1对抗CD3诱导的胸腺细胞[Ca ̄(2+)]i应答的影响。结果显示,可溶性抗LFA-1/ICAM-1可抑制ConA刺激的胸腺细胞增殖,且以抗LFA-1抗体的作用更为显著,在ConA或抗CD3诱导的胸腺细胞[Ca ̄(2+)]i应答中,抗LFA-1单抗可明显抑制[Ca ̄(2+)i升高。但如果用二抗交联CD3和LFA-1,胸腺细胞[Ca ̄(2+)i则显著高于单独交联CD3时的水平(P<0.01),而CD3与ICAM-l交联却无此效应,此外,仅交联LFA-1或ICAM-1也无诱导[Ca ̄(2+)]i应答的作用。提示在LFA-l与ICAM-1介导的胸腺细胞与胸腺基质细胞相互作用中,LFA-1可为TCR/CD3途径介导的胸腺细胞活化提供复合刺激信号。

【Abstract】 ymphocyte function-associated antigen(LFA-1)and its ligand intercellular adhesion molecule-l(ICAM-1)were expressed on each thymocyte subpopulation, but the expression of ICAM-1on the PNA+ subset was down-regulated.The early signaling events involved in the activation of thymocytes were analyzed by[Ca2+]i(intercellu-lar free calcium concentration)response of thymocytes triggered by anti-CD3 antibody to determine the contribu-tion by the LFA-1/ICAM-1interaction. Thc results showed that soluble anti-LFA-1or anti-ICAM-1antibodies could inhibit the proliferation of thymocytes upon Con A stimulation ,and the inhibitory effect of anti-LFA-1 was more significant than anti-ICAM-1. When anti-LFA-1was added to the Con A-or immobilized anti- CD3-stimulat-ed thymocyte cultures,a remarkable decrease in the intercellular levels of free Ca2+ was observed.However,thecross-linking of CD3 with LFA-1 by secondary antibodies resulted in the elevation in [Ca2+]i, and this increase was m uch higher than that induced by cross-linked CD3 alone (P<0.01 ). But this effect was not exhibited bycross-linking CD3 and ICAM-1.In addition,it was unable to induce[Ca2+]i response in thymocytes by cross-link-ing LFA-1/ICAM-1alone. Thus,thc necessary costimulation required for CD3-mediated proliferation of thymo-cytes in this model system may be provided by the LFA-1/ICAM-l interaction which in combination with anti-CD3 leads to signal-transduction events.

【基金】 美国洛氏基金会CMB基金,国家自然科学基金
  • 【文献出处】 中华微生物学和免疫学杂志 ,CHINESE JOURNAL OF MICROBIOLOGY AND IMMUNOLOGY , 编辑部邮箱 ,1994年05期
  • 【分类号】R392.12
  • 【下载频次】17
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