Kropf P, Etges R, Schopf L, Chung C, Sypek J, Müller I
Department of Biological Sciences, University of Notre Dame, IN 46556, USA.
J Immunol. 1997 Oct 1;159(7):3434-43.
IL-4 drives polarized Th2 responses, and differentiating Th2 cells down-regulate their sensitivity to IL-12. Therefore, the failure of BALB/c mice to heal Leishmania major infection could be due to an IL-4-dependent biased Th2 response or to a reduced capacity of Leishmania-specific Th cells to respond to IL-12. We examined the ability of CD4+ Th cells from L. major-infected wild-type and IL-4-deficient BALB/c mice to respond to IL-12. We show that the inability of normal and IL-4-deficient BALB/c mice to heal L. major infections is due to their inability to generate effective Th1 responses and not to persistent IL-4-dominated Th2 responses. Redirection of immune responses in vivo by administration of IL-12 or anti-CD4 mAb treatment in the early phase of infection (+/-12 days) allows both normal and IL-4-deficient BALB/c mice to heal their lesions by allowing them to develop an efficient Th1 response regardless of the presence or the absence of IL-4. Finally, on a population level, Ag-specific Th cells from infected animals induced to heal display a strongly elevated response to IL-12.
白细胞介素-4驱动极化的辅助性T细胞2（Th2）反应，而正在分化的Th2细胞会下调其对白细胞介素-12的敏感性。因此，BALB/c小鼠无法治愈硕大利什曼原虫感染，可能是由于白细胞介素-4依赖的偏向性Th2反应，或者是利什曼原虫特异性Th细胞对白细胞介素-12反应的能力降低。我们检测了来自感染硕大利什曼原虫的野生型和白细胞介素-4缺陷型BALB/c小鼠的CD4⁺ Th细胞对白细胞介素-12的反应能力。我们发现，正常和白细胞介素-4缺陷型BALB/c小鼠无法治愈硕大利什曼原虫感染，是由于它们无法产生有效的Th1反应，而不是由于持续存在以白细胞介素-4为主导的Th2反应。在感染早期（±12天）通过给予白细胞介素-12或抗CD4单克隆抗体治疗在体内重定向免疫反应，可使正常和白细胞介素-4缺陷型BALB/c小鼠通过产生有效的Th1反应来治愈其损伤，而无论是否存在白细胞介素-4。最后，在群体水平上，来自被诱导治愈的感染动物的抗原特异性Th细胞对白细胞介素-12的反应强烈增强。
