Guiñazú Natalia, Pellegrini Andrea, Giordanengo Laura, Aoki Maria P, Rivarola Hector W, Cano Roxana, Rodrigues Mauricio M, Gea Susana
Inmunología, Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, Haya de la Torre y Medina Allende S/N, 5000 Córdoba, Argentina.
Microbes Infect. 2004 Nov;6(14):1250-8. doi: 10.1016/j.micinf.2004.07.010.
BALB/c mice immunized with cruzipain, a major Trypanosoma cruzi antigen, produce specific and autoreactive immune responses against heart myosin, associated with cardiac functional and structural abnormalities. Preferential activation of the Th2 phenotype and an increase in cell populations expressing CD19+, Mac-1+ and Gr-1+ markers were found in the spleens of these mice. The aim of the present study was to investigate whether cardiac autoimmunity could be induced by cruzipain immunization of C57BL/6 mice and to compare the immune response elicited with that of BALB/c mice. We demonstrate that immune C57BL/6 splenocytes, re-stimulated in vitro with cruzipain, produced high levels of IFNgamma and low levels of IL-4 compatible with a Th1 profile. In contrast to BALB/c mice, spleens from cruzipain immune C57BL/6 mice revealed no significant changes in the number of cells presenting CD19+, Mac-1+ and Gr-1+ markers. An increased secretion of TGFbeta and a greater number of CD4+ TGFbeta+ cells were found in immune C57BL/6 but not in BALB/c mice. These findings were associated with the lack of autoreactive response against heart myosin and a myosin- or cruzipain-derived peptide. Thus, the differential immune response elicited in C57BL/6 and BALB/c mice upon cruzipain immunization is implicated in the resistance or pathogenesis of experimental Chagas' disease.
用克氏锥虫主要抗原克鲁斯蛋白酶免疫的BALB/c小鼠会产生针对心肌肌球蛋白的特异性自身反应性免疫反应,这与心脏功能和结构异常有关。在这些小鼠的脾脏中发现了Th2表型的优先激活以及表达CD19+、Mac-1+和Gr-1+标志物的细胞群体增加。本研究的目的是调查用克鲁斯蛋白酶免疫C57BL/6小鼠是否能诱导心脏自身免疫,并将引发的免疫反应与BALB/c小鼠的进行比较。我们证明,用克鲁斯蛋白酶在体外再次刺激的免疫C57BL/6脾细胞产生了高水平的IFNγ和低水平的IL-4,符合Th1型特征。与BALB/c小鼠不同,来自用克鲁斯蛋白酶免疫的C57BL/6小鼠的脾脏中,呈现CD19+、Mac-1+和Gr-1+标志物的细胞数量没有显著变化。在免疫的C57BL/6小鼠中发现TGFβ分泌增加且CD4+ TGFβ+细胞数量更多,而在BALB/c小鼠中未发现。这些发现与缺乏针对心肌肌球蛋白和肌球蛋白或克鲁斯蛋白酶衍生肽的自身反应性反应有关。因此,C57BL/6和BALB/c小鼠在用克鲁斯蛋白酶免疫后引发的不同免疫反应与实验性恰加斯病的抗性或发病机制有关。