Karulin Alexey Y, Hesse Maike D, Yip Hualin C, Lehmann Paul V
Department of Pathology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
J Immunol. 2002 Jan 15;168(2):545-53. doi: 10.4049/jimmunol.168.2.545.
Recall Ag-specific IL-4 was detected in the spleen and in the blood, but not in lymph nodes of mice in which polarized type 1 immunity was induced. This IL-4 was not produced by T cells, but soluble factors secreted by the recall Ag-activated T cells, including IL-3, triggered cells of the innate immune system, primarily mast cells, to secrete IL-4. This notion has profound implications for immunodiagnostics: the detection of apparently recall Ag-specific IL-4 does not necessarily reflect the presence of Th2 or Th0 memory T cells with long-term cytokine commitment as is of interest for assessing adoptive immunity. We found that in vivo the indirect IL-4 pathway did not suffice to trigger IgE isotype switching, but promoted IgG1 production and inhibited type 1 T cell differentiation. Therefore, the indirect IL-4 pathway can explain partial type 2 immune response phenotypes in vivo in face of unipolar Th1 T cell immunity. The representation of mast cells in different tissues may explain why immune responses in certain organs are more type 2 biased. Therefore, the indirect pathway of IL-4 production represents a novel type of interaction between the innate and the adoptive immune system that can contribute to the outcome of host defense and immune pathology.
在诱导了极化1型免疫的小鼠脾脏和血液中检测到了回忆抗原特异性白细胞介素-4（IL-4），但在淋巴结中未检测到。这种IL-4不是由T细胞产生的，而是由回忆抗原激活的T细胞分泌的可溶性因子，包括IL-3，触发先天免疫系统的细胞，主要是肥大细胞，分泌IL-4。这一概念对免疫诊断具有深远意义：检测到明显的回忆抗原特异性IL-4不一定反映具有长期细胞因子分泌能力的辅助性T细胞2型（Th2）或辅助性T细胞0型（Th0）记忆T细胞的存在，而这对于评估过继性免疫是有意义的。我们发现，在体内，间接IL-4途径不足以触发免疫球蛋白E（IgE）同种型转换，但促进了免疫球蛋白G1（IgG1）的产生并抑制了1型T细胞分化。因此，间接IL-4途径可以解释在面对单极性辅助性T细胞1型（Th1）免疫时体内部分2型免疫反应表型。不同组织中肥大细胞的分布可能解释了为什么某些器官中的免疫反应更偏向2型。因此，IL-4产生的间接途径代表了先天免疫系统和过继性免疫系统之间一种新型的相互作用，这种相互作用可能影响宿主防御和免疫病理的结果。
