Poussin Mathilde A, Tüzün Erdem, Goluszko Elzbieta, Scott Benjamin G, Yang Huan, Franco Juan U, Christadoss Premkumar
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.
J Immunol. 2003 Apr 15;170(8):4389-96. doi: 10.4049/jimmunol.170.8.4389.
Following immunization with acetylcholine receptor (AChR), MHC class II-restricted, AChR-specific CD4 cell activation is critical for the development of experimental autoimmune myasthenia gravis (EAMG) in C57BL/6 mice. To study the contributions of B7-1 and B7-2 costimulatory molecules in EAMG, B7-1, B7-2, and B7-1/B7-2 gene knockout (KO) mice were immunized with Torpedo AChR in CFA. Compared with wild-type C57BL6 mice, B7-1 and B7-1/2 KO mice were resistant to EAMG development. B7-1 KO mice had reduced anti-AChR Ab compared with C57BL/6 mice. However, neither B7-1 nor B7-2 gene disruption impaired AChR-induced or dominant alpha(146-162) peptide-induced in vitro lymphoproliferative responses. Blocking of the B7-1 or B7-2 molecule by specific mAbs in vivo led to a reduction in the AChR-specific lymphocyte response, and the reduction was more pronounced in mice treated with anti-B7-2 Ab. The findings implicate B7-1 molecules as having a critical role in the induction of EAMG, and the resistance of B7-1 KO mice is associated with suppressed humoral, rather than suppressed AChR-specific, T cell responses. The data also point to B7-2 molecules as being the dominant costimulatory molecules required for AChR-induced lymphocyte proliferation.
在用乙酰胆碱受体（AChR）免疫后，MHC II类限制性、AChR特异性CD4细胞活化对于C57BL/6小鼠实验性自身免疫性重症肌无力（EAMG）的发展至关重要。为了研究B7-1和B7-2共刺激分子在EAMG中的作用，将B7-1、B7-2和B7-1/B7-2基因敲除（KO）小鼠在完全弗氏佐剂中用鱼雷AChR免疫。与野生型C57BL6小鼠相比，B7-1和B7-1/2 KO小鼠对EAMG发展具有抗性。与C57BL/6小鼠相比，B7-1 KO小鼠的抗AChR抗体减少。然而，B7-1和B7-2基因破坏均未损害AChR诱导的或显性α（146-162）肽诱导的体外淋巴细胞增殖反应。体内用特异性单克隆抗体阻断B7-1或B7-2分子导致AChR特异性淋巴细胞反应减少，在用抗B7-2抗体处理的小鼠中这种减少更明显。这些发现表明B7-1分子在EAMG诱导中起关键作用，并且B7-1 KO小鼠的抗性与体液反应抑制有关，而不是与AChR特异性T细胞反应抑制有关。数据还表明B7-2分子是AChR诱导的淋巴细胞增殖所需的主要共刺激分子。
