Fas ligand (CD95L) and B7 expression on dendritic cells provide counter-regulatory signals for T cell survival and proliferation.
Fas ligand (CD95L) and B7 expression on dendritic cells provide counter-regulatory signals for T cell survival and proliferation.
复制标题
DOI：
10.4049/jimmunol.158.12.5676
复制
发表时间：
1997-06
影响因子：
4.4
通讯作者：
Lina Lu;S. Qian;P. Hershberger;W. Rudert;David H. Lynch;A. Thomson
中科院分区：
文献类型：
--
作者：
Lina Lu;S. Qian;P. Hershberger;W. Rudert;David H. Lynch;A. Thomson
树突状细胞(DC)能有效地诱导T细胞活化，但对DC在T细胞死亡调控中的作用知之甚少。本研究通过逆转录聚合酶链式反应和免疫细胞化学分析发现，从正常小鼠骨髓培养的高纯度DC(DEC-205+、MHC II类(高)、B7-1+[CD80+]、B7-2High[CD86高]、CD40+、CD11c+)在粒细胞-巨噬细胞集落刺激因子+IL-4中表达FasL(CD95L)mRNA，并通过流式细胞仪和免疫细胞化学分析均可表达FasL。这些细胞，而不是来自FasL缺陷(B6.gld)小鼠的DC，在18h的共同培养中诱导Fas+Jurkat T细胞DNA片段化，呈剂量依赖性增加。在培养开始时加入小鼠Fas-Fc融合蛋白可以减弱这种影响。然而，即使在较高的相对浓度下，B7-2高DC也只能诱导ConA或同种异体脾T细胞的低水平DNA片段化，如放射或荧光分析和原位缺口末端标记所确定的那样。然而，在阻断B7-CD28共刺激通路的分子CTLA4Ig的存在下，在原代MLR中未能刺激的DC诱导同种异体激活的T细胞的凋亡水平显著增加。CTLA4Ig处理还增加了FasL缺陷DC诱导的DNA片段化水平，表明DC诱导T细胞死亡存在额外的潜在(Fas不依赖)途径。这些发现表明，共刺激(B7-CD28)和T细胞死亡诱导通路可能在决定(同种)DC-T细胞相互作用的结果中发挥重要的反调节作用。
Activation of T cells is induced efficiently by dendritic cells (DC), but little is known about the role of DC in the regulation of T cell death. In this study, highly purified DC (DEC-205+, MHC class II(high), B7-1+ [CD80+], B7-2high [CD86high], CD40+, CD11c+) grown from normal mouse bone marrow in granulocyte-macrophage CSF + IL-4 were found to express FasL (CD95L) mRNA by reverse transcriptase PCR and to uniformly express FasL by both flow cytometric and immunocytochemical analyses. These cells, but not DC propagated from FasL-deficient (B6.gld) mice, induced dose-dependent increases in DNA fragmentation in Fas+ Jurkat T cells over 18 h coculture. Addition of mouse Fas-Fc fusion protein at the start of the cultures diminished this effect. Even at high relative concentrations, however, B7-2high DC induced only low levels of DNA fragmentation in Con A or alloactivated splenic T cells, as determined by radio- or spectrofluorometric assays and by in situ nick-end labeling. However, in the presence of CTLA4Ig, a molecule that blocks the B7-CD28 costimulatory pathway, DC that failed to stimulate in primary MLR induced markedly augmented levels of apoptosis in alloactivated T cells. CTLA4Ig treatment also increased the level of DNA fragmentation induced by FasL-deficient DC, indicating the existence of additional potential (Fas-independent) pathways of DC-induced T cell death. These findings suggest that the costimulatory (B7-CD28) and T cell death-inducing pathways may play important counter-regulatory roles in dictating the outcome of (allogeneic) DC-T cell interactions.