High frequency of cross-reactive cytotoxic T lymphocytes elicited during the virus-induced polyclonal cytotoxic T lymphocyte response.
High frequency of cross-reactive cytotoxic T lymphocytes elicited during the virus-induced polyclonal cytotoxic T lymphocyte response.
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DOI：
10.1084/jem.177.2.317
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发表时间：
1993-02-01
期刊：
影响因子：
--
通讯作者：
Welsh RM
中科院分区：
文献类型：
--
作者：
Nahill SR;Welsh RM
CD 8+细胞毒性T淋巴细胞（CTL）的多克隆刺激发生在许多病毒感染期间，包括那些未知的转化CTL或编码超抗原。这种多克隆CTL应答包括产生针对许多I类单倍型的高水平同种特异性CTL。在这份报告中，我们调查是否产生的同种异体特异性CTL在急性淋巴细胞性脉络丛脑膜炎病毒（LCMV）感染C57 BL/6小鼠刺激特异性抗原识别或非特异性多克隆机制可能涉及淋巴因子或超抗原。对不同品系小鼠诱导高水平的同种异体抗原特异性CTL的能力的研究表明，大多数（但不是所有）品系产生高水平的同种异体特异性CTL，并且它们产生这些CTL的能力在遗传上映射到主要组织相容性复合体位点，排除II类区域。这表明，病毒诱导的同种异体CTL的产生是独立的II类同种异型，和小鼠耗尽的CD 4+细胞产生同种异体CTL，表明独立的II类-CD 4+细胞的相互作用和产生的CD 4+细胞分泌的淋巴因子。用多种V β结合抗体进行的FACS染色在感染期间未显示任何测试的V β +亚群的超抗原样耗尽或富集。几个实验提供了支持通过T细胞受体直接刺激CD 8+细胞的证据：（a）在给定的V β亚群中富集了病毒特异性和同种异体特异性杀伤;（B）在病毒感染过程中，针对不同I类同种异体抗原的相对CTL前体频率发生了变化;（c）感染后第8天病毒诱导的同种特异性CTL介导的裂解的相对水平与感染前的CTL前体频率不平行;和（d）用病毒感染的同系腹膜渗出细胞（PEC）刺激的第8天LCMV感染的脾细胞的有限稀释分析不仅揭示了预期的病毒特异性CTL克隆，而且与同种异体和病毒感染的同基因靶交叉反应的克隆频率高。除了病毒交叉反应的同种特异性CTL克隆，病毒感染的PEC也刺激产生一些同种特异性克隆，不裂解病毒感染的成纤维细胞。令人惊讶的是，LCMV感染的PEC在刺激来自第8天LCMV感染的脾细胞的同种异体特异性CTL克隆方面比同种异体刺激剂有效得多。这些结果表明，由急性病毒感染引起的多克隆同种特异性CTL应答的至少一部分是与病毒感染的细胞交叉反应的同种特异性CTL的许多克隆的选择性扩增的结果。（400字处截断摘要）
Polyclonal stimulation of CD8+ cytotoxic T lymphocytes (CTL) occurs during infection with many viruses including those not known to transform CTL or encode superantigens. This polyclonal CTL response includes the generation of high levels of allospecific CTL directed against many class I haplotypes. In this report we investigated whether the allospecific CTL generated during an acute lymphocytic choriomeningitis virus (LCMV) infection of C57BL/6 mice were stimulated specifically by antigen recognition or nonspecifically by polyclonal mechanisms possibly involving lymphokines or superantigens. An examination of the ability of different strains of mice to induce high levels of CTL specific for a given alloantigen showed that most, but not all, strains generated high levels of allospecific CTL, and that their abilities to generate them mapped genetically to the major histocompatibility complex locus, exclusive of the class II region. This indicated that the virus-induced allospecific CTL generation was independent of the class II allotype, and mice depleted of CD4+ cells generated allospecific CTL, indicating independence of class II-CD4+ cell interactions and resulting CD4+ cell-secreted lymphokines. FACS staining with a variety of V beta-binding antibodies did not show a superantigen-like depletion or enrichment of any tested V beta + subset during infection. Several experiments provided evidence in support of direct stimulation of CD8+ cells via the T cell receptor: (a) both virus- and allo-specific killing were enriched within a given V beta subpopulation; (b) relative CTL precursor frequencies against different class I alloantigens changed during the course of virus infection; (c) the relative levels of virus-induced, allospecific CTL-mediated lysis at day 8 after infection did not parallel the CTL precursor frequencies before infection; and (d) limiting dilution analyses of day 8 LCMV- infected spleen cells stimulated by virus-infected syngeneic peritoneal exudate cells (PEC) revealed not only the expected virus-specific CTL clones, but also a high frequency of clones that were cross-reactive with allogeneic and virus-infected syngeneic targets. In addition to the virus cross-reactive allospecific CTL clones, virus-infected PEC also stimulated the generation of some allospecific clones that did not lyse virus-infected fibroblasts. Surprisingly, LCMV-infected PEC were much more efficient at stimulating allospecific CTL clones from day 8 LCMV-infected splenocytes than were allogeneic stimulators. These results indicate that at least part of the polyclonal allospecific CTL response elicited by acute virus infection is a consequence of the selective expansion of many clones of allospecific CTL which cross- react with virus-infected cells.(ABSTRACT TRUNCATED AT 400 WORDS)
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DOI：
10.1073/pnas.75.6.2844
发表时间：
1978-01-01
影响因子：
11.1
作者：
WYSOCKI, LJ;SATO, VL
通讯作者：
SATO, VL
影响因子：
5.4
作者：
STRANG, G;RICKINSON, AB
通讯作者：
RICKINSON, AB
影响因子：
3.7
作者：
WELSH, RM;LAMPERT, PW;OLDSTONE, MBA
通讯作者：
OLDSTONE, MBA
影响因子：
5.4
作者：
MOSKOPHIDIS, D;ASSMANNWISCHER, U;LEHMANNGRUBE, F
通讯作者：
LEHMANNGRUBE, F
影响因子：
8.7
作者：
MACDONALD, HR;GLASEBROOK, AL;CEROTTINI, JC
通讯作者：
CEROTTINI, JC