Gause W C, Lu P, Zhou X D, Chen S J, Madden K B, Morris S C, Linsley P S, Finkelman F D, Urban J F
Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, USA.
Exp Parasitol. 1996 Nov;84(2):264-73. doi: 10.1006/expr.1996.0112.
The gastrointestinal nematode parasite, Heligmosomoides polygyrus, has been used extensively in experimental studies of host immunity. The pronounced type 2 primary immune response to H. polygyrus is associated with elevated CD4+, TCR-alpha/beta + T cell IL-4 production and elevated serum IgE levels that are blocked by inhibiting CD28/ CTLA4-B7 interactions following in vivo administration of the chimeric fusion protein, CTLA4Ig. In the present study, we have examined the in vivo effects of blocking CTLA4Ig ligands on the secondary type 2 mucosal host protective immune response to this parasite. Our results show that although CD4+, TCR-alpha/beta + cells remain the primary source of elevated IL-4 during the secondary response, the protective immune response and the effector cell activity associated with it is B7-independent as CTLA4Ig administration at the time of challenge does not block (1) elevations in T cell IL-4 gene expression or protein secretion; (2) elevations in serum IgE levels, mucosal mastocytosis, or eosinophilia; or (3) host protection, as measured by adult worm burden and fecundity. These findings suggest that memory T helper cells do not require CD28-B7 interactions for their activation to effector cells that can mediate a host protective type 2 immune response.
胃肠道线虫寄生虫多房棘球绦虫已被广泛用于宿主免疫的实验研究。对多房棘球绦虫明显的2型初次免疫反应与CD4⁺、TCR-α/β⁺ T细胞IL-4产生增加以及血清IgE水平升高有关，在体内给予嵌合融合蛋白CTLA4Ig后，通过抑制CD28/CTLA4-B7相互作用可阻断这些反应。在本研究中，我们研究了阻断CTLA4Ig配体对宿主针对该寄生虫的2型黏膜二次保护性免疫反应的体内影响。我们的结果表明，虽然在二次反应期间CD4⁺、TCR-α/β⁺细胞仍然是IL-4升高的主要来源，但与之相关的保护性免疫反应和效应细胞活性不依赖于B7，因为在攻击时给予CTLA4Ig不会阻断：（1）T细胞IL-4基因表达或蛋白质分泌的升高；（2）血清IgE水平升高、黏膜肥大细胞增多或嗜酸性粒细胞增多；或（3）通过成虫虫负荷和繁殖力衡量的宿主保护。这些发现表明，记忆性辅助性T细胞激活为可介导宿主保护性2型免疫反应的效应细胞时不需要CD28-B7相互作用。
