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蛋白质抗原特异性Ia限制的细胞毒性T细胞:频率、靶细胞敏感性及细胞溶解机制分析

Protein-antigen specific Ia-restricted cytolytic T cells: analysis of frequency, target cell susceptibility, and mechanism of cytolysis.

作者信息

Tite J P, Powell M B, Ruddle N H

出版信息

J Immunol. 1985 Jul;135(1):25-33.

PMID:2582034
Abstract

We previously showed that cloned, antigen-specific, Ia-restricted L3T4a+ T cell lines can be cytolytic for antigen-pulsed B cell lymphoma targets. Such cells can also, under different experimental conditions, activate B cells to proliferate and secrete immunoglobulin. In the present experiments, we show that this functional phenotype is a common one among a panel of cloned T cell lines. In keeping with this finding, freshly isolated, antigen-activated lymph node T cells show similar functional properties. Such cytolytic L3T4a+ T cells differ from classical H-2K/D-restricted cytolytic T cells in two distinct ways. First, Ia-restricted cytolytic T cells can kill bystander targets, whereas H-2K/D-specific cytolytic T cells do not. Second, in testing a panel of target cells by using lectin-mediated cytolysis, Ia-restricted cytolytic clones reveal large differences in target cell susceptibility, whereas all targets are similarly susceptible to H-2K/D-specific killer cells. Finally, evidence is presented that both direct and bystander killing effected by L3T4a+ T cells are mediated by the same soluble factors, in that there is a strong positive correlation of these two activities for individual cloned lines. The relevant mediators appear to be lymphotoxin and IFN-gamma, although the latter molecule by itself is not cytolytic on our target lines.

摘要

我们先前表明,克隆的、抗原特异性的、受Ia限制的L3T4a+ T细胞系可对脉冲抗原的B细胞淋巴瘤靶标产生细胞毒性。在不同实验条件下,这类细胞还能激活B细胞增殖并分泌免疫球蛋白。在本实验中,我们表明这种功能表型在一组克隆的T细胞系中很常见。与此发现一致,新鲜分离的、抗原激活的淋巴结T细胞表现出相似的功能特性。这类具有细胞毒性的L3T4a+ T细胞与经典的受H-2K/D限制的细胞毒性T细胞在两个不同方面存在差异。第一,受Ia限制的细胞毒性T细胞可杀伤旁观者靶标,而H-2K/D特异性细胞毒性T细胞则不能。第二,在用凝集素介导的细胞溶解法检测一组靶细胞时,受Ia限制的细胞毒性克隆显示出靶细胞敏感性存在很大差异,而所有靶标对H-2K/D特异性杀伤细胞的敏感性相似。最后,有证据表明L3T4a+ T细胞所产生的直接杀伤和旁观者杀伤均由相同的可溶性因子介导,因为对于单个克隆系而言,这两种活性存在很强的正相关性。相关介质似乎是淋巴毒素和干扰素-γ,尽管后一种分子本身对我们的靶细胞系无细胞毒性。

相似文献

1
Protein-antigen specific Ia-restricted cytolytic T cells: analysis of frequency, target cell susceptibility, and mechanism of cytolysis.蛋白质抗原特异性Ia限制的细胞毒性T细胞:频率、靶细胞敏感性及细胞溶解机制分析
J Immunol. 1985 Jul;135(1):25-33.
2
Distinct proliferative T cell clonotypes are generated in response to a murine retrovirus-induced syngeneic T cell leukemia: viral gp70 antigen-specific MT4+ clones and Lyt-2+ cytolytic clones which recognize a tumor-specific cell surface antigen.针对小鼠逆转录病毒诱导的同基因T细胞白血病,会产生不同的增殖性T细胞克隆型:病毒gp70抗原特异性MT4 +克隆和识别肿瘤特异性细胞表面抗原的Lyt-2 +溶细胞克隆。
J Immunol. 1985 Jul;135(1):703-13.
3
Cloned helper T cells can kill B lymphoma cells in the presence of specific antigen: Ia restriction and cognate vs. noncognate interactions in cytolysis.克隆化辅助性T细胞在存在特异性抗原的情况下可杀伤B淋巴瘤细胞:细胞溶解中的Ia限制以及同源与非同源相互作用
Eur J Immunol. 1984 Oct;14(10):878-86. doi: 10.1002/eji.1830141004.
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Different phenotypic variants of the mouse B cell tumor A20/2J are selected by antigen- and mitogen-triggered cytotoxicity of L3T4-positive, I-A-restricted T cell clones.小鼠B细胞肿瘤A20/2J的不同表型变体是由L3T4阳性、I-A限制的T细胞克隆的抗原和丝裂原触发的细胞毒性所选择的。
J Immunol. 1986 Jan;136(1):348-56.
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Anti-tumor activity of class II MHC antigen-restricted cloned autoreactive T cells. I. Destruction of B16 melanoma cells mediated by bystander cytolysis in vitro.II类主要组织相容性复合体抗原限制的克隆自身反应性T细胞的抗肿瘤活性。I. 体外旁观者细胞溶解介导的B16黑色素瘤细胞破坏。
J Immunol. 1987 Mar 15;138(6):1971-8.
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Hapten-specific, class II-restricted killing by cloned T cells: direct lysis and production of a cytotoxic factor.克隆化T细胞对半抗原特异性的、Ⅱ类分子限制的杀伤作用:直接裂解及细胞毒因子的产生。
J Immunol. 1986 Apr 15;136(8):2826-31.
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Cytolytic activity of antigen-specific T cells with helper phenotype.具有辅助细胞表型的抗原特异性T细胞的细胞溶解活性。
J Immunol. 1986 Jan;136(1):44-7.
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A rat anti-mouse T4 monoclonal antibody (H129.19) inhibits the proliferation of Ia-reactive T cell clones and delineates two phenotypically distinct (T4+, Lyt-2,3-, and T4-, Lyt-2,3+) subsets among anti-Ia cytolytic T cell clones.一种大鼠抗小鼠T4单克隆抗体(H129.19)可抑制Ia反应性T细胞克隆的增殖,并在抗Ia细胞毒性T细胞克隆中区分出两个表型不同的亚群(T4+、Lyt-2,3-和T4-、Lyt-2,3+)。
J Immunol. 1984 Jun;132(6):2775-82.
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The immunobiology of T cell responses to Mls-locus-disparate stimulator cells. III. Helper and cytolytic functions of cloned, Mls-reactive T cell lines.
J Immunol. 1986 Jan;136(1):1-5.
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CD4+ T cell-mediated killing of MHC class II-positive antigen-presenting cells. I. Characterization of target cell recognition by in vivo or in vitro activated CD4+ killer T cells.CD4 + T细胞介导的MHC II类阳性抗原呈递细胞的杀伤作用。I. 体内或体外活化的CD4 +杀伤性T细胞对靶细胞识别的特征
J Immunol. 1990 Feb 1;144(3):790-5.

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Analysis of cytotoxic activity of the CD4+ T lymphocytes generated by local immunotherapy.局部免疫疗法产生的CD4 + T淋巴细胞的细胞毒性活性分析。
Br J Cancer. 1996 Jan;73(1):110-6. doi: 10.1038/bjc.1996.20.
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In vivo lymphokine production in experimental autoimmune uveoretinitis.实验性自身免疫性葡萄膜视网膜炎中的体内淋巴因子产生
Immunology. 1993 Mar;78(3):387-92.
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Altered peptide ligands can control CD4 T lymphocyte differentiation in vivo.改变的肽配体可在体内控制CD4 T淋巴细胞分化。
J Exp Med. 1995 Apr 1;181(4):1569-74. doi: 10.1084/jem.181.4.1569.
5
Direct interactions between B and T lymphocytes bearing complementary receptors.携带互补受体的B淋巴细胞和T淋巴细胞之间的直接相互作用。
J Exp Med. 1986 Jan 1;163(1):189-202. doi: 10.1084/jem.163.1.189.
6
Tumor necrosis factor and immune interferon act in concert to slow the lateral diffusion of proteins and lipids in human endothelial cell membranes.肿瘤坏死因子和免疫干扰素协同作用,减缓人内皮细胞膜中蛋白质和脂质的侧向扩散。
J Cell Biol. 1988 Aug;107(2):781-9. doi: 10.1083/jcb.107.2.781.
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Two types of mouse helper T cell clone. III. Further differences in lymphokine synthesis between Th1 and Th2 clones revealed by RNA hybridization, functionally monospecific bioassays, and monoclonal antibodies.两种小鼠辅助性T细胞克隆。III. 通过RNA杂交、功能单特异性生物测定法和单克隆抗体揭示的Th1和Th2克隆在淋巴因子合成方面的进一步差异。
J Exp Med. 1987 Nov 1;166(5):1229-44. doi: 10.1084/jem.166.5.1229.
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Heterogeneous cytotoxic cells that kill NC-sensitive WEHI-164 tumor cells are activated in allogeneic mixed lymphocyte reactions.在同种异体混合淋巴细胞反应中,可杀伤对NC敏感的WEHI-164肿瘤细胞的异质性细胞毒性细胞被激活。
Immunol Res. 1986;5(1):40-9. doi: 10.1007/BF02917193.
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Autocrine growth inhibition of a cloned line of helper T cells.辅助性T细胞克隆系的自分泌生长抑制
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DNA fragmentation: manifestation of target cell destruction mediated by cytotoxic T-cell lines, lymphotoxin-secreting helper T-cell clones, and cell-free lymphotoxin-containing supernatant.DNA片段化:由细胞毒性T细胞系、分泌淋巴毒素的辅助性T细胞克隆以及含有无细胞淋巴毒素的上清液介导的靶细胞破坏的表现。
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