Chatelain R, Varkila K, Coffman R L
Department of Immunology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA 94304.
J Immunol. 1992 Feb 15;148(4):1182-7.
The infection of mice with Leishmania major can cause either a fatal disseminated disease or a localized healing disease, depending on the genetic background of the mice. A strong correlation has been shown between disease outcome and the nature of the T cell response, with healer strains developing a Th1-like response and nonhealer strains a Th2-like response. The treatment of nonhealer BALB/c mice with a single dose of an anti-IL-4 antibody, given at the time of infection with L. major, allowed these mice to develop healing Th1-like responses, suggesting that IL-4 is required in BALB/c mice for the differentiation of Th cells into Th2 cells. Anti-IL-4 had to be present during the first 2 wk of infection to have this effect. Anti-IL-4 caused a marked shift from a Th2 to a Th1 pattern of cytokine expression within 4 days, in vivo, and injections of IL-4 had the opposite effect on the early response in healer C3H/HeN mice. These findings demonstrate that IL-4 can induce the development of Th2 response to L. major infection in vivo.
根据小鼠的遗传背景，用硕大利什曼原虫感染小鼠可导致致命的播散性疾病或局部愈合性疾病。疾病结局与T细胞反应的性质之间已显示出强烈的相关性，愈合型品系产生类似Th1的反应，非愈合型品系产生类似Th2的反应。在用硕大利什曼原虫感染时给非愈合型BALB/c小鼠单次注射抗IL-4抗体，可使这些小鼠产生愈合性的类似Th1的反应，这表明在BALB/c小鼠中，IL-4是Th细胞分化为Th2细胞所必需的。抗IL-4必须在感染的前2周内存在才能产生这种效果。抗IL-4在体内4天内使细胞因子表达模式从Th2型明显转变为Th1型，而注射IL-4对愈合型C3H/HeN小鼠的早期反应有相反的作用。这些发现表明，IL-4可在体内诱导对硕大利什曼原虫感染的Th2反应的发展。
