Sacks T, Klinman D M
Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA.
Cell Immunol. 1997 May 1;177(2):162-8. doi: 10.1006/cimm.1997.1114.
Specific antigen/adjuvant combinations preferentially induce type 1 or type 2 cytokine responses. For example, BALB/c mice primed with TNP-ovalbumin in complete Freund's adjuvant (TNP-OVA/CFA) produce a type 2-dominated response characterized by the activation of IL-4-secreting cells and the production of IgG1 and IgE anti-TNP antibodies. In contrast, mice primed with TNP conjugated to Brucella abortus (TNP-BA) produce a type 1 response dominated by the secretion of IFN-gamma and IgG2a anti-TNP antibodies. We examined whether treating young mice with these antigen/adjuvant combinations altered the cytokine profile of their subsequent immune responses. Mice immunized with TNP-BA and boosted several months later with TNP-OVA/CFA developed a cytokine and antibody profile similar to the priming rather than boosting antigen. This was also observed in mice immunized with TNP-OVA/CFA and boosted with TNP-BA. Both the ratio of IL-4:IFN-gamma-secreting cells and the isotype of antibodies produced by these mice were altered by primary immunization. Analysis of Con A-responsive cells from these animals showed that long-lived changes in the frequency of T lymphocytes available to secrete type 1 versus type 2 cytokines were induced by strong primary immunogens.
特定的抗原/佐剂组合优先诱导1型或2型细胞因子反应。例如，用完全弗氏佐剂（TNP-OVA/CFA）中的TNP-卵清蛋白免疫的BALB/c小鼠产生以分泌IL-4的细胞活化以及产生IgG1和IgE抗TNP抗体为特征的2型主导反应。相比之下，用与流产布鲁氏菌偶联的TNP（TNP-BA）免疫的小鼠产生以IFN-γ分泌和IgG2a抗TNP抗体为主导的1型反应。我们研究了用这些抗原/佐剂组合处理幼鼠是否会改变其后续免疫反应的细胞因子谱。用TNP-BA免疫并在几个月后用TNP-OVA/CFA加强免疫的小鼠产生的细胞因子和抗体谱类似于初次免疫而非加强免疫的抗原。在用TNP-OVA/CFA免疫并用TNP-BA加强免疫的小鼠中也观察到了这种情况。这些小鼠分泌IL-4:IFN-γ的细胞比例以及产生的抗体亚型均因初次免疫而改变。对这些动物的刀豆蛋白A反应性细胞的分析表明，强的初次免疫原可诱导分泌1型与2型细胞因子的T淋巴细胞频率发生长期变化。
