Barbosa de Oliveira L C, Curotto de Lafaille M A, Collet de Araujo Lima G M, de Almeida Abrahamsohn I
Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, Brazil.
Cell Immunol. 1996 May 25;170(1):41-53. doi: 10.1006/cimm.1996.0132.
Control of macrophage parasiticidal function by treatment with recombinant cytokines or their neutralizing antibodies modifies the severity of experimental Trypanosoma cruzi infections. However, so far, no direct in vivo evidence has demonstrated changes in disease outcome after altering the initial ratios of parasite-specific IFN-gamma and IL-10/IL-4-secretor cells in secondary lymphoid organs. To this end, a population of predominantly CD4+ parasite-Ag-reactive, IL-4- and IL-10-secreting T lymphocytes derived from T. cruzi-immunized mice was adoptively transferred to naive recipients. Compared with cell responses from normal mice, spleen cells of uninfected recipients proliferated significantly to T. cruzi Ag and produced much greater amounts of IL-4 and IL-10; lower IFN-gamma levels and increased IL-4/IL-10 levels were induced by Con A stimulation. Recipient mice challenged with T. cruzi presented overwhelming tissue and blood parasitemia and early death, contrasting with typically resistant controls. Uninfected recipients did not exhibit tissue damage following cell transfer. No disease exacerbation occurred in recipients of OVA-reactive CD4+, IL-4/IL-10-secreting T lymphocytes stimulated with OVA at the start of infection. On Day 6 postinfection, not only spleen cells but also LN cells from infected recipients showed decreased production of IFN-gamma and augmented secretion of IL-4/IL-10 compared to cells from untransferred infected mice. The results indicate that an imbalance of Th cell populations leading to the predominance of secreted IL-4 and IL-10 at the start of infection and the concomitant down-regulation of IFN-gamma secretion reversed the host's resistance to T. cruzi. Moreover, transfer of anti-T. cruzi Th2-type cells most likely favored the in vivo expansion of parasite-specific host cells toward a Th2 phenotype.
用重组细胞因子或其中和抗体处理来控制巨噬细胞的杀寄生虫功能，可改变实验性克氏锥虫感染的严重程度。然而，迄今为止，尚无直接的体内证据表明，改变次级淋巴器官中寄生虫特异性干扰素-γ和白细胞介素-10/白细胞介素-4分泌细胞的初始比例后，疾病结局会发生变化。为此，将一群主要来自克氏锥虫免疫小鼠的、具有寄生虫抗原反应性、分泌白细胞介素-4和白细胞介素-10的CD4⁺ T淋巴细胞过继转移给未感染的受体。与正常小鼠的细胞反应相比，未感染受体的脾细胞对克氏锥虫抗原有显著增殖，并产生大量白细胞介素-4和白细胞介素-10；用刀豆蛋白A刺激可诱导较低的干扰素-γ水平和升高的白细胞介素-4/白细胞介素-10水平。用克氏锥虫攻击的受体小鼠出现严重的组织和血液寄生虫血症并早期死亡，这与通常具有抗性的对照形成对比。未感染的受体在细胞转移后未表现出组织损伤。在感染开始时用卵清蛋白刺激的、具有卵清蛋白反应性的CD4⁺、分泌白细胞介素-4/白细胞介素-10的T淋巴细胞受体小鼠未出现疾病加重。感染后第6天，与未转移感染小鼠的细胞相比，感染受体的脾细胞和淋巴结细胞不仅干扰素-γ产生减少，白细胞介素-4/白细胞介素-10分泌增加。结果表明，Th细胞群体的失衡导致感染开始时分泌的白细胞介素-4和白细胞介素-10占优势，同时干扰素-γ分泌下调，从而逆转了宿主对克氏锥虫的抗性。此外，抗克氏锥虫Th2型细胞的转移最有可能有利于寄生虫特异性宿主细胞在体内向Th2表型的扩增。
