NONCYTOTOXIC HUMAN CD4(+) T-CELL CLONES PRESENTING AND SIMULTANEOUSLY RESPONDING TO AN ANTIGEN DIE OF APOPTOSIS
NONCYTOTOXIC HUMAN CD4(+) T-CELL CLONES PRESENTING AND SIMULTANEOUSLY RESPONDING TO AN ANTIGEN DIE OF APOPTOSIS
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DOI：
10.1006/cimm.1995.1010
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发表时间：
1995-03-01
影响因子：
4.3
通讯作者：
WYSSCORAY, T
中科院分区：
文献类型：
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作者：
BETTENS, F;FREI, E;WYSSCORAY, T
表达MHC II类表面抗原的活化t细胞能够呈递抗原，因此具有肽呈递细胞（T-APCs）的功能。在这项研究中，我们研究了t细胞抗原呈递是否会诱导程序性细胞死亡。我们使用破伤风p30肽（aa 947-967）特异性、非细胞毒性CD4(+) t细胞克隆（C11和C31）作为模型。为了实验目的，这些t细胞克隆被(a)用p30肽脉冲和固定的ebv转化抗原提呈细胞（b -APCs）刺激，(b)用p30脉冲和固定的活化t细胞作为APCs（作为T-APCs，我们使用t细胞克隆本身或具有p30无关特异性的自体t细胞克隆（CT3）），或(c)用可溶性p30肽刺激。通过测量[H-3]胸腺嘧啶摄取的增殖来监测抗原呈递的效率。用荧光染料4,6-二氨基-2-苯基吲哚定量测定细胞质DNA片段，或用凝胶电泳观察DNA片段。用p30脉冲和固定的B-APCs或T-APCs刺激可诱导t细胞增殖，但未引起t细胞凋亡。然而，用可溶性肽刺激克隆的t细胞可诱导FAS表面分子的上调和凋亡，这与肽剂量有关。由于克隆的t细胞表达HLAⅱ类分子，在可溶性肽刺激下，理论上可以同时发挥抗原呈递和抗原应答两种功能。由于凋亡死亡只在这种情况下才会出现，我们认为t细胞同时呈递和应答抗原死于细胞凋亡，从而有助于免疫反应的下调。在HIV感染中，激活的CD4(+) t细胞通过其CD4分子吸收gp120，将其呈递到HLA II类表面抗原上，同时通过其TCR受到刺激，可能会发生这种现象。(C) 1995学术出版社，Inc。
Activated T-cells expressing MHC class II surface antigens are able to present antigen and thus function as peptide-presenting cells (T-APCs). In this study we investigated whether antigen presentation by T-cells induced programmed cell death. As a model we used tetanus p30 peptide (aa 947-967)-specific, noncytotoxic CD4(+) T-cell clones (C11 and C31). For experimental purposes these T-cell clones were stimulated (a) with p30 peptide-pulsed and fixed EBV-transformd antigen-presenting cells (B-APCs), (b) with p30-pulsed and fixed activated T-cells as APCs (as T-APCs we used either the T-cell clones themselves or an autologous T-cell clone (CT3) with p30 unrelated specificity), or (c) with soluble p30 peptide. The efficiency of antigen presentation was monitored by measuring proliferation as [H-3]thymidine uptake. Apoptosis was measured by quantifying fragmented, cytoplasm DNA with the fluorescent dye 4,6-diamidino-2-phenylindole or by visualizing fragmented DNA by gel electrophoresis. Stimulation with p30-pulsed and fixed B-APCs or T-APCs induced proliferation but no apoptosis of the responding T-cells. However, stimulation of cloned T-cells with soluble peptide induced up-regulation of the FAS surface molecules and apoptosis, which was dependent on the peptide doses. Because cloned T-cells express HLA class II molecules, they can theoretically exert both functions at once: antigen presentation and antigen response when they are stimulated with soluble peptide. Because death by apoptosis is only seen under such circumstances, we suggest that T-cells simultaneously presenting and responding to an antigen die of apoptosis and thus contribute to the down-regulation of the immune response. Such phenomena might occur in HIV infection when activated CD4(+) T-cells take up gp120 via their CD4 molecules, present it on their HLA class II surface antigens, and are simultaneously stimulated via their TCR. (C) 1995 Academic Press, Inc.