Viral and bacterial infections interfere with peripheral tolerance induction and activate CD8+ T cells to cause immunopathology.
Viral and bacterial infections interfere with peripheral tolerance induction and activate CD8+ T cells to cause immunopathology.
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病毒和细菌感染会干扰周围耐受性诱导并激活CD8+ T细胞引起免疫病理学。
DOI：
10.1084/jem.187.5.763
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发表时间：
1998-03-02
影响因子：
15.3
通讯作者：
Pircher, H
中科院分区：
文献类型：
--
作者：
Ehl, S;Hombach, J;Aichele, P;Rülicke, T;Odermatt, B;Hengartner, H;Zinkernagel, R;Pircher, H
我们研究了各种感染和促炎剂对诱导外周T细胞耐受的影响。将CD 8 + T细胞从淋巴细胞性脉络丛脑膜炎病毒（LCMV）T细胞受体转基因小鼠连续转移到在主要组织相容性复合物I类启动子控制下表达LCMV糖蛋白表位（gp）33-41的LCMV抗原转基因小鼠中，导致在短暂激活一段时间后有效诱导外周耐受。然而，如果受体小鼠在细胞转移后早期用病毒或细菌感染或促炎剂（脂多糖或Poly：IC）攻击，则耐受诱导被阻止，相反，CD 8 + T细胞活化导致剧烈扩增并产生细胞溶解活性。这在显著的免疫病理学中变得明显，主要涉及脾结构的破坏和抗原表达淋巴细胞和巨噬细胞群的溶解。参与非特异性感染因子激活宿主反应性T细胞的重要参数包括特异性转基因编码的自身抗原的存在、定位和数量;相反，不需要CD 4 + T细胞。在急性期存活的小鼠中，转移的CD 8 + T细胞在无反应性状态下持续高水平;它们无法在体外产生细胞溶解活性或在体内控制LCMV感染。这些结果影响了我们对感染因子在移植物抗宿主反应中对次要组织相容性抗原的作用的理解。
We studied the impact of various infectious and proinflammatory agents on the induction of peripheral T cell tolerance. Adoptive transfer of CD8+ T cells from lymphocytic choriomeningitis virus (LCMV) T cell receptor transgenic mice into LCMV antigen transgenic mice expressing the LCMV glycoprotein epitope (gp) 33–41 under control of a major histocompatibility complex class I promoter led to efficient induction of peripheral tolerance after a period of transient activation. If, however, the recipient mice were challenged with viral or bacterial infections or proinflammatory agents (lipopolysaccharide or Poly:IC) early after cell transfer, tolerance induction was prevented and instead, CD8+ T cell activation leading to vigorous expansion and generation of cytolytic activity ensued. This became manifest in significant immunopathology mainly involving destruction of the splenic architecture and lysis of antigen-expressing lymphocyte and macrophage populations. Important parameters involved in the activation of host-reactive T cells by nonspecific infectious agents included the presence, localization, and quantity of the specific transgene-encoded self-antigen; in contrast, CD4+ T cells were not required. In mice surviving the acute phase, the transferred CD8+ T cells persisted at high levels in an anergic state; they were unable to generate cytolytic activity in vitro or to control LCMV infection in vivo. These results impinge on our understanding of the role of infectious agents in graft verus host reactions towards minor histocompatibility antigens.
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DOI：
10.1084/jem.183.6.2645
发表时间：
1996-06-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Baker MB;Altman NH;Podack ER;Levy RB
通讯作者：
Levy RB
DOI：
10.1084/jem.176.2.553
发表时间：
1992-08-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Guerder S;Matzinger P
通讯作者：
Matzinger P
通过抗原和细菌脂多糖（内毒素）终止小鼠对人丙种球蛋白的耐受性。
DOI：
10.1084/jem.137.3.740
发表时间：
1973-03-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Chiller JM;Weigle WO
通讯作者：
Weigle WO
影响因子：
64.8
作者：
KAGI, D;LEDERMANN, B;HENGARTNER, H
通讯作者：
HENGARTNER, H
DOI：
10.1084/jem.138.6.1481
发表时间：
1973-12-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Louis JA;Chiller JM;Weigle WO
通讯作者：
Weigle WO