Jeannin P, Herbault N, Delneste Y, Magistrelli G, Lecoanet-Henchoz S, Caron G, Aubry J P, Bonnefoy J Y
Centre d'Immunologie Pierre Fabre, Saint-Julien en Genevois, France.
J Immunol. 1999 Feb 15;162(4):2044-8.
The glycoprotein CD86 expressed on APCs provides a costimulatory signal necessary for an efficient activation of naive T cells. In contrast, there is controversy about the condition of expression and the function of CD86 on T cells. In this study, we have analyzed the phenotype and the biological activity of CD86+ T cells generated from human PBMC. Results show that CD86 expression on T cells is induced by long term stimulation via CD3 and IL-2R and is down-regulated as the cells become quiescent. The CD86-expressing cells are memory effector T cells: 1) they express CD45RO and high levels of the activation markers CD25, CD54, and HLA-Dr; 2) they selectively express CD30, CD40-ligand, and CD70; and 3) in response to stimulation, most of them produce IFN-gamma before dying by apoptosis. We then analyzed whether CD86 expressed on T cells is functional. Results show that paraformaldehyde-fixed CD86+ T cells enhance the proliferation and production of IFN-gamma by anti-CD3 mAb-stimulated naive T cells and induce proliferation of resting allogenic T cells. All these effects are prevented by neutralizing anti-CD86 mAbs. In contrast, we report no autocrine effect of CD86 in CD86+ T cell activation. In conclusion, these data show that human memory effector T cells express a functional form of CD86 that can costimulate naive T cell responses.
抗原呈递细胞(APCs)上表达的糖蛋白CD86为初始T细胞的有效激活提供了共刺激信号。相比之下,关于CD86在T细胞上的表达情况及其功能存在争议。在本研究中,我们分析了从人外周血单个核细胞(PBMC)产生的CD86+ T细胞的表型和生物学活性。结果显示,T细胞上的CD86表达是由通过CD3和IL-2R的长期刺激诱导产生的,并且随着细胞进入静止状态而下调。表达CD86的细胞是记忆效应T细胞:1)它们表达CD45RO以及高水平的激活标志物CD25、CD54和HLA-Dr;2)它们选择性地表达CD30、CD40配体和CD70;3)在受到刺激时,它们中的大多数在通过凋亡死亡之前产生干扰素-γ。然后我们分析了T细胞上表达的CD86是否具有功能。结果显示,经多聚甲醛固定的CD86+ T细胞可增强抗CD3单克隆抗体刺激的初始T细胞的增殖和干扰素-γ的产生,并诱导静息同种异体T细胞的增殖。所有这些效应都可被中和性抗CD86单克隆抗体阻断。相比之下,我们报告CD86在CD86+ T细胞激活中没有自分泌效应。总之,这些数据表明人类记忆效应T细胞表达一种功能性形式的CD86,它可以共刺激初始T细胞反应。