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TRAIL/Apo-2配体在活化小鼠T细胞和B细胞中的表面表达。

Surface expression of TRAIL/Apo-2 ligand in activated mouse T and B cells.

作者信息

Mariani S M, Krammer P H

机构信息

Division of Immunogenetics, German Cancer Research Center, Heidelberg.

出版信息

Eur J Immunol. 1998 May;28(5):1492-8. doi: 10.1002/(SICI)1521-4141(199805)28:05<1492::AID-IMMU1492>3.0.CO;2-X.

Abstract

Like other members of the TNF family, TRAIL/Apo-2 ligand induces apoptosis in sensitive target cells in a caspase-dependent fashion. We recently found that TRAIL may be constitutively expressed on the surface of mouse and human tumor cells of T and B origin. To define the pattern of TRAIL expression in normal immune cells, freshly isolated splenocytes, Concanavalin A/IL-2-activated T cells and lipopolysaccharide-activated B cells were analyzed by surface staining with or without secondary stimulation. Activated, but not resting, CD3+ cells expressed TRAIL in an activation-dependent fashion. Conversely, freshly isolated B220+ cells displayed surface TRAIL and CD95L that were retained following activation. Restimulation with the protein kinase C activator phorbol 12-myristate 13-acetate and the calcium ionophore ionomycin or an agonistic anti-CD3 monoclonal antibody induced significant up-regulation of surface TRAIL and CD95L in CD3+, TCRalphabeta cells with CD4+ or CD8+ phenotype. Similarly to CD95L, TRAIL up-regulation was protein synthesis dependent and cyclosporin A sensitive. These results indicate that both TRAIL and CD95L are displayed on the cell surface of activated immune cells and may thus represent complementary effector pathways in the regulatory functions of T and B cells.

摘要

与肿瘤坏死因子(TNF)家族的其他成员一样,肿瘤坏死因子相关凋亡诱导配体(TRAIL)/Apo-2配体以半胱天冬酶依赖性方式诱导敏感靶细胞凋亡。我们最近发现,TRAIL可能在源自T和B的小鼠及人类肿瘤细胞表面组成性表达。为了确定正常免疫细胞中TRAIL的表达模式,我们通过有无二次刺激的表面染色分析了新鲜分离的脾细胞、伴刀豆球蛋白A/白细胞介素-2激活的T细胞和脂多糖激活的B细胞。活化的而非静止的CD3⁺细胞以激活依赖性方式表达TRAIL。相反,新鲜分离的B220⁺细胞表面显示有TRAIL和CD95L,且在激活后仍保留。用蛋白激酶C激活剂佛波醇12-肉豆蔻酸酯13-乙酸酯和钙离子载体离子霉素或抗CD3单克隆抗体进行再刺激,可诱导具有CD4⁺或CD8⁺表型的CD3⁺、TCRαβ细胞表面TRAIL和CD95L显著上调。与CD95L类似,TRAIL上调依赖于蛋白质合成且对环孢素A敏感。这些结果表明,TRAIL和CD95L均在活化免疫细胞的细胞表面表达,因此可能代表T细胞和B细胞调节功能中的互补效应途径。

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