Da Silva A C, Espinoza A G, Taibi A, Ouaissi A, Minoprio P
Department of Immunology, Pasteur Institute, Paris, France.
Immunology. 1998 Jun;94(2):189-96. doi: 10.1046/j.1365-2567.1998.00498.x.
Trypanosoma cruzi, the causative agent of Chagas' disease, is a protozoan parasite that infects humans and other mammals in Central and Latin America. Several alterations of the immune response after infection have been described, such as severe immunosuppression of both cellular and humoral responses and massive polyclonal B- and T-cell activation, including the expansion of self-reactive clones. We have investigated the effects of the intraperitoneal injection of a recombinant 24,000 MW T. cruzi-specific antigen (rTc24) on the immune response of normal and deficient strains of mice. We analysed the in vivo and ex vivo levels of lymphocyte activation and the proliferative responses to rTc24 by determining the expression of CD69 activation marker and the levels of thymidine incorporation by spleen cells. The numbers of antibody-producing cells were determined by ELISPOT and the levels of immunoglobulin in the sera by isotype-specific enzyme-linked immunosorbent assay. We observed an increased [3H]thymidine ([3H]TdR) incorporation by spleen cells after rTc24 stimulation in vivo and in vitro. This proliferative activity induced by rTc24 was independent of the mouse strain used in the experiments (including C3H/HeJ mice) and ruled out the possibility that rTc24 preparations were contaminated by lipopolysaccharide. The injection of rTc24 protein induced preferentially the activation of B cells, as determined by the increased expression of CD69 molecules on IgM+ spleen cells. Considerable increases of IgM-secreting B cells were determined in both athymic and euthymic BALB/c mice. Mice that are deficient in B cells (BALB.Xid) responded to rTc24 but to a lesser extent. These increases in IgM B-cell numbers were accompanied by elevated levels of IgM immunoglobulins in the sera of injected animals. Our results suggest a role for rTc24 in B-cell activation.
克氏锥虫是恰加斯病的病原体,是一种原生动物寄生虫,可感染中美洲和拉丁美洲的人类及其他哺乳动物。感染后免疫反应的几种改变已被描述,例如细胞和体液反应的严重免疫抑制以及大量多克隆B细胞和T细胞的激活,包括自身反应性克隆的扩增。我们研究了腹腔注射重组24,000 MW克氏锥虫特异性抗原(rTc24)对正常和缺陷小鼠品系免疫反应的影响。我们通过测定CD69激活标志物的表达以及脾细胞掺入胸苷的水平,分析了淋巴细胞激活的体内和体外水平以及对rTc24的增殖反应。通过ELISPOT测定产生抗体的细胞数量,通过同型特异性酶联免疫吸附测定法测定血清中的免疫球蛋白水平。我们观察到在体内和体外rTc24刺激后脾细胞掺入[3H]胸苷([3H]TdR)增加。rTc24诱导的这种增殖活性与实验中使用的小鼠品系无关(包括C3H/HeJ小鼠),并排除了rTc24制剂被脂多糖污染的可能性。如通过IgM +脾细胞上CD69分子表达的增加所确定的,rTc24蛋白的注射优先诱导B细胞的激活。在无胸腺和有胸腺的BALB/c小鼠中均测定到分泌IgM的B细胞有相当大的增加。缺乏B细胞的小鼠(BALB.Xid)对rTc24有反应,但程度较小。IgM B细胞数量的这些增加伴随着注射动物血清中IgM免疫球蛋白水平的升高。我们的结果表明rTc24在B细胞激活中起作用。