CD4 T lymphocytes are primed to express Fas ligand by CD4 cross-linking and to contribute to CD8 T-cell apoptosis via Fas/FasL death signaling pathway

作     者：Tateyama, M Oyaizu, N McCloskey, TW Than, S Pahwa, S 

作者机构：NYU N Shore Univ Hosp Dept Pediat Sch MedDiv Allergy Immunol Manhasset NY 11030 USA Tokyo Med & Dent Univ Dept Retroviral Regulat Div Med Res Bunkyo Ku Tokyo Japan 

出 版 物：《BLOOD》 (血液)

年 卷 期：2000年第96卷第1期

页      面：195-202页

核心收录：

学科分类：1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 10[医学] 

基　　金：NIAID NIH HHS [AI28281] Funding Source: Medline NIDA NIH HHS [DA05161] Funding Source: Medline 

主　　题：抗原 CD/免疫学 抗原 CD3/免疫学 抗原 CD4/免疫学 抗原 CD95/免疫学 细胞凋亡/免疫学 CD4阳性T淋巴细胞/免疫学 CD4阳性T淋巴细胞/生理学 CD8阳性T淋巴细胞/细胞学 CD8阳性T淋巴细胞/免疫学 CD8阳性T淋巴细胞/生理学 Fas配体蛋白质 干扰素Ⅱ型/生物合成 淋巴细胞活化 膜糖蛋白类/遗传学 膜糖蛋白类/免疫学 RNA 信使/遗传学 逆转录聚合酶链反应 信号传导/免疫学 肿瘤坏死因子α/生物合成 人类 

摘      要：CD4 molecules serve as coreceptors for the T-cell receptor (TCR)/CD3 complex that are engaged coordinately with TCR and facilitate antigen-specific T-cell activation leading to interleukin 2 (IL-2) production and proliferation. However, cross-ligation of CD4 molecules prior to TCR stimulation has been shown to prime CD4 T cells to undergo apoptosis. Although in vivo and in vitro experiments have implicated the involvement of Fas/FasL interaction in this CD4 cross-linking (CD4XL)-induced apoptosis, detailed mechanisms to account for cell death induction have not been elucidated. In the present study, we demonstrate that CD4XL in purified T cells not only led to Fas up-regulation but also primed CD4 T cells to express Fast upon CD3 stimulation and rendered the T cells susceptible to Fas mediated apoptosis. Notably, in addition to CD4(+) T cells, CD4XL-induced sensitization for apoptosis was observed in CD8(+) T cells as well and was associated with Bcl-x down-modulation. Both CD4 and CD8 T-cell subsets underwent apoptosis following cell-cell contact with FasL(+) CD4 T cells. CD28 costimulation abrogated CD4XL/ CD3-induced apoptosis with restoration of IL-2 production and prevented Bcl-x down-modulation. As CD4 molecules are the primary receptors for human immunodeficiency virus 1 (HIV-1), we conclude that HIV-1 envelope mediated CD4XL can lead to the generation of FasL-expressing CD4+ T cells that can lead to apoptosis of CD4 as well as CD8 T cells. These findings implicate a novel mechanism for CD8 T-cell depletion in HIV disease. (Blood. 2000;98:195-202) (C) 2000 by The American Society of Hematology.