Th2 activities induced during virgin T cell priming in the absence of IL-4, IL-13, and B cells

Th2 activities induced during virgin T cell priming in the absence of IL-4, IL-13, and B cells
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DOI:
10.4049/jimmunol.169.6.2900
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发表时间:
2002-09-15
影响因子:
4.4
通讯作者:
Toellner, KM
Toellner, KM
中科院分区:
医学2区
文献类型:
--
作者:
Cunningham, AF;Fallon, PG;Toellner, KM

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分别用Th 2诱导性或Th 1诱导性Ag致敏的原始T细胞在它们开始增殖时开始合成IL-4或IFN-γ。平行地分别诱导B细胞产生γ 1或γ 2a转换转录物提供了早期趋异Th活性的额外证据。本报告关注IL-4、IL-13和B细胞在这些早期体内事件中的作用。在淋巴结中诱导针对s.c.给予的半抗原蛋白的Th 2应答。用灭活的百日咳杆菌佐剂。在野生型小鼠的T细胞增殖中,IL-4信息上调以及γ 1和γ开关转录物产生在免疫后进行48-72 111。IL-4、IL-13或B细胞的缺乏并没有改变早期T细胞增殖反应。在IL-4、IL-13或两者均不存在的情况下,γ 1和IgG 1开关转录物的产生仍被诱导,但水平降低,而在滤泡外半抗原特异性浆细胞反应中切换至IgG 1的优势被保留。在不存在B细胞的情况下,IL-4信息的上调没有减少或延迟,并且在不存在IL-13的情况下仅略微减少。结论是树突状细胞传递的信号,这是不依赖于IL-4,IL-13,或B细胞的存在下,可以引发处女T细胞和诱导研究的早期Th 2活动。这些引导原始T细胞向Th 2分化的早期事件与Th 2细胞因子在选择性扩增Th 2克隆和驱动进一步IL-4合成中的关键后期作用形成对比。
Virgin T cells being primed to Th2-inducing or Th1-inducing Ags, respectively, start to synthesize IL-4 or IFN-gamma as they begin to proliferate. Parallel respective induction of B cells to produce gamma1 or gamma2a switch transcripts provides additional evidence of early divergent Th activity. This report concerns the roles of IL-4, IL-13, and B cells in these early events in vivo. Th2 responses were induced in lymph nodes against hapten-protein given s.c. with killed Bordetella pertussis adjuvant. In T cell proliferation in wild-type mice, IL-4 message up-regulation and gamma1 and epsilon switch transcript production were underway 48-72 111 after immunization. The absence of IL-4, IL-13, or B cells did not alter the early T cell proliferative response. The gamma1 and epsilon switch transcript production was still induced in the absence of IL-4, IL-13, or both, but at a reduced level, while the dominance of switching to IgG1 in the extrafollicular hapten-specific plasma cell response was retained. The up-regulation of IL-4 message was not reduced or delayed in the absence of B cells and was only marginally reduced by the absence of IL-13. It is concluded that signals delivered by dendritic cells, which are not dependent on the presence of IL-4, IL-13, or B cells, can prime virgin T cells and induce the early Th2 activities studied. These early events that direct virgin T cells toward Th2 differentiation contrast with the critical later role of Th2 cytokines in selectively expanding Th2 clones and driving further IL-4 synthesis.