Antigen dose-dependent suppression of murine IgE responses is mediated by CD4-CD8- double-negative T cells
Antigen dose-dependent suppression of murine IgE responses is mediated by CD4-CD8- double-negative T cells
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DOI：
10.1111/j.1365-2222.2010.03476.x
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发表时间：
2010-06-01
影响因子：
6.1
通讯作者：
Sudowe, S.
中科院分区：
文献类型：
--
作者：
Barwig, C.;Raker, V.;Sudowe, S.
背景 对蛋白抗原的 IgE 反应很大程度上受致敏剂量的影响。 目的 本研究的目的是鉴定参与抗原剂量依赖性调节 IgE 形成的免疫细胞。 方法 通过重复腹腔注射低剂量（K01小鼠）或高剂量（K100 小鼠）吸附于氢氧化铝的匙孔血蓝蛋白。在体外重新刺激免疫小鼠的脾细胞，并测量抗原依赖性 T 细胞增殖和细胞因子的产生。使用荧光细胞术和 RT-PCR 分析比较 K01 和 K100 小鼠脾细胞中调节性 T 细胞亚群的频率。将脾细胞或 T 细胞亚群转移到初始小鼠中，并在用低抗原剂量引发受体后确定淋巴细胞转移对 IgE 产生的影响。结果 K100 小鼠中特异性 IgE 产生显着受损。抗原再刺激显示 K100 脾细胞增殖不足，Th2 细胞因子 IL-4、IL-5 和 IL-13 的产生减少，但没有诱导 IFN-γ 的产生。此外，K01和K100小鼠的淋巴细胞在与常规调节性T细胞的表型或活性相关的分子表达方面没有表现出显着差异。来自 K100 小鼠的脾细胞或纯化 T 细胞的转移以抗原和同种型特异性方式显着抑制了受体中 IgE 产生的诱导。 K100小鼠的CD4(+)和CD8(+) T细胞均不能抑制IgE形成；相反，我们确定 CD4(-)CD8(-) 双阴性 T 细胞 (dnT 细胞) 为主要 T 细胞群，可有效抑制 IgE 的产生。结论我们的数据表明 CD4(-)CD8(-) dnT 细胞在调节高抗原剂量诱导的 IgE 反应中发挥着重要作用。
Background The IgE response against protein antigens is profoundly influenced by the dose used for sensitization.Objective The aim of the study was to identify immune cells that are involved in antigen dose-dependent regulation of IgE formation.Methods Wild-type mice as well as T helper (Th) 1-deficient IL-12p40(-/-) and IFN-gamma(-/-) mice were immunized by repeated intraperitoneal injection of either low doses (K01 mice) or high doses (K100 mice) of keyhole limpet haemocyanin adsorbed to aluminium hydroxide. Splenocytes of immunized mice were restimulated in vitro and antigen-dependent T cell proliferation and cytokine production were measured. The frequency of regulatory T cell subsets among splenocytes from K01 and K100 mice was compared using fluorocytometry and RT-PCR analysis. Splenocytes or T cell subpopulations were transferred into naive mice and the effect of lymphocyte transfer on IgE production after priming of recipients with low antigen doses was determined.Results Specific IgE production was considerably impaired in K100 mice. Antigenic restimulation revealed hypoproliferation of K100 splenocytes and reduced production of Th2 cytokines IL-4, IL-5 and IL-13, but no induction of IFN-gamma production. Moreover, lymphocytes from K01 and K100 mice did not show significant differences in the expression of molecules associated with the phenotype or activity of conventional regulatory T cells. Transfer of splenocytes or purified T cells from K100 mice substantially suppressed the induction of IgE production in the recipients in an antigen- and isotype-specific manner. Neither CD4(+) nor CD8(+) T cells from K100 mice were able to inhibit IgE formation; instead, we identified CD4(-)CD8(-) double-negative T cells (dnT cells) as the principal T cell population, which potently suppressed IgE production.Conclusion Our data demonstrate that CD4(-)CD8(-) dnT cells play a major role in the regulation of IgE responses induced by high antigen doses.