Heinzel F P, Sadick M D, Mutha S S, Locksley R M
Department of Medicine, University of California, San Francisco 94143-0654.
Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7011-5. doi: 10.1073/pnas.88.16.7011.
The expression of interleukin (IL) 2, IL-4, IL-10, and interferon gamma (IFN-gamma) by lymphocyte subsets was examined during infection of resistant C57BL/6 and susceptible BALB/c mice with the protozoan parasite Leishmania major. CD4+ and CD8+ T lymphocytes and B lymphocytes were isolated from the lymph nodes draining infectious lesions, and their RNA was examined for lymphokine transcripts. Distinct patterns of CD4+ cell cytokine expression were apparent: C57BL/6 CD4+ cells contained IFN-gamma and IL-2 mRNA, whereas BALB/c CD4+ cells expressed IL-4 and IL-10 message. CD8+ cells contributed little lymphokine expression during disease, but B cells were a major source of IL-2 mRNA in both strains of mice. BALB/c mice made resistant by treatment with anti-CD4 antibody at the time of infection repopulated lymph nodes with CD4+ cells that expressed IL-2 and IFN-gamma. Protective treatment with anti-IL-4 antibody in vivo also resulted in the appearance of CD4+ cells with increased IFN-gamma and diminished IL-4 and IL-10 expression. These data establish CD4+ cells as the primary source of IFN-gamma in healing mice and of IL-4 and IL-10 during progressive infection and confirm that the spectral extremes of this disease are characterized by the presence of CD4+ cells expressing Th1 or Th2 phenotypes in vivo.
在用原生动物寄生虫硕大利什曼原虫感染抗性C57BL/6小鼠和易感BALB/c小鼠的过程中，检测了淋巴细胞亚群白细胞介素（IL）-2、IL-4、IL-10和干扰素γ（IFN-γ）的表达。从引流感染病灶的淋巴结中分离出CD4⁺和CD8⁺ T淋巴细胞以及B淋巴细胞，并检测其RNA中的淋巴因子转录本。CD4⁺细胞细胞因子表达的明显不同模式：C57BL/6 CD4⁺细胞含有IFN-γ和IL-2 mRNA，而BALB/c CD4⁺细胞表达IL-4和IL-10信息。在疾病过程中，CD8⁺细胞的淋巴因子表达很少，但在两种品系小鼠中，B细胞都是IL-2 mRNA的主要来源。在感染时用抗CD4抗体治疗而产生抗性的BALB/c小鼠，其淋巴结中重新填充了表达IL-2和IFN-γ的CD4⁺细胞。体内用抗IL-4抗体进行保护性治疗也导致出现IFN-γ增加、IL-4和IL-10表达减少的CD4⁺细胞。这些数据确定CD4⁺细胞是愈合小鼠中IFN-γ的主要来源，是进行性感染期间IL-4和IL-10的主要来源，并证实该疾病的两个极端情况在体内的特征是存在表达Th1或Th2表型的CD4⁺细胞。
