CD4+ T-CELL-MEDIATED KILLING OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II-POSITIVE ANTIGEN-PRESENTING CELLS (APC) .3. CD4+ CYTOTOXIC T-CELLS INDUCE APOPTOSIS OF APC
CD4+ T-CELL-MEDIATED KILLING OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II-POSITIVE ANTIGEN-PRESENTING CELLS (APC) .3. CD4+ CYTOTOXIC T-CELLS INDUCE APOPTOSIS OF APC
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DOI：
10.1002/eji.1830220139
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发表时间：
1992-01-01
影响因子：
5.4
通讯作者：
ERB, P
中科院分区：
文献类型：
--
作者：
GROGG, D;HAHN, S;ERB, P
CD 4 + T细胞的一个子集属于1型辅助性T细胞（T（h）1）细胞，以抗原特异性和主要组织相容性复合体（MHC）II类限制性方式杀死抗原递呈细胞（APC）。 有证据表明，CD 4+细胞毒性T淋巴细胞（CTL）诱导细胞凋亡或程序性细胞死亡内易感APC作为见证的定量DNA片段。 细胞凋亡比Cr-51释放试验更可靠地确定细胞死亡，因为一些细胞在Cr-51释放试验中表现出对CD 4介导的裂解的抗性。 细胞凋亡在靶细胞崩解前孵育2至4小时后变得明显，这在12至24小时之间可检测到，如通过Cr-51释放测定所测量的。 未受刺激的B细胞，其不被杀死，但作为APC发挥作用，不经历细胞凋亡，而脂多糖或抗mu活化的B细胞母细胞显示细胞凋亡并被有效地裂解。 几种测试的CD 4 + T（h）2型细胞，如通过Cr-51-释放测定所测量的，其没有显示APC的杀伤，不能介导适当APC的程序性细胞死亡。 放线菌素D或放线菌酮，转录和翻译的抑制剂，分别未能防止APC细胞凋亡，排除参与新合成的可溶性产物作为介质的杀伤。 用阴离子转运的特异性抑制剂4，4 '-二异硫氰酸基芪-2，2'-二磺酸预处理CD 4 + CTL，而不是APC，有效地防止APC的凋亡，尽管白细胞介素的分泌不受影响。 我们建议，在接触的CD 4 + CTL与APC，分子尚未定义的性质被激活，并释放在一个极性的方式在接触部位，并诱导内源性途径的程序性细胞死亡。
A subset of CD4+ T cells, belonging to the T helper type 1 (T(h)1) cells, kills antigen-presenting cells (APC) in an antigen-specific and major histocompatibility complex (MHC) class II-restricted way. Evidence is presented that CD4+ cytotoxic T lymphocytes (CTL) induce apoptosis or programmed cell death within susceptible APC as witnessed by quantitative DNA fragmentation. Apoptosis is more reliable to determine cell death than the Cr-51-release assay, because some cells demonstrate resistance to CD4-mediated lysis in the Cr-51-release assay. Apoptosis becomes manifest after 2 to 4 h of incubation preceding the disintegration of the target cells which is detectable between 12 and 24 h as measured by the Cr-51-release assay. Unstimulated B cells, which are not killed, but function as APC, do not undergo apoptosis, whereas lipopolysaccharide or anti-mu-activated B cell blasts show apoptosis and are efficiently lysed. Several CD4+ T(h)2-type cells tested, which did not demonstrate killing of APC as measured by the Cr-51-release assay, are unable to mediate programmed cell death of appropriate APC. Actinomycin D or cycloheximide, inhibitors of transcription and translation, respectively, fail to prevent apoptosis of APC excluding the involvement of newly synthesized soluble products as mediators of killing. Pretreatment of CD4+ CTL, but not of APC with 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid, a specific inhibitor of the anion transport, efficiently prevents apoptosis of APC, although the secretion of interleukins is not affected. We propose, that upon contact of the CD4+ CTL with APC, molecules of yet undefined nature are activated and released in a polar fashion at the contact site and induce the endogenous pathway of programmed cell death.