Peptide-induced anergy in allergen-specific human Th2 cells results in lack of cytokine production and B cell help for IgE synthesis. Reversal by IL-2, not by IL-4 or IL-13.
Peptide-induced anergy in allergen-specific human Th2 cells results in lack of cytokine production and B cell help for IgE synthesis. Reversal by IL-2, not by IL-4 or IL-13.
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过敏原特异性人类 Th2 细胞中肽诱导的无反应性导致缺乏细胞因子产生和 B 细胞对 IgE 合成的帮助。
作者：
Stephan Fasler;G. Aversa;A. Terr;Kristian Thestrup;J. D. Vries;H. Yssel
T细胞的能量诱导被认为是在CD28及其配体CD80和CD86相互作用介导的缺乏足够共刺激的情况下触发TCR的结果。在这里，我们证明了在没有专业APC的情况下，用Der p1衍生的肽刺激人I组过敏原在翼状胬肉提取物（Der p1）中特异性CD4+ th2样T细胞克隆的结果是无反应状态。尽管T细胞克隆表面表达了高水平的CD28、CD80和CD86，但能量的诱导仍然发生，并且不能通过添加抗CD28单抗来阻止。在Der p 1衍生肽和自体APC的最佳刺激下，无能的、Der p 1特异性的Th2细胞无法从细胞内储存中动员钙，无法增殖，也无法产生IL-2、IL-4、IL-13、GM-CSF和tnf - α。然而，它们在受到Ca(2+)-离子载体刺激后动员细胞内钙，并在受到磷酯和Ca2+离子载体刺激时产生上述所有细胞因子，包括ifn - γ。这些结果表明，无能T细胞克隆能够响应绕过TCR/CD3复合物激活途径的信号。与最佳激活肽和APC的T细胞克隆相比，当与B细胞共培养时，即使存在外源性IL-4或IL-13，无能T细胞也不能诱导IgG4和IgE合成。无能T细胞表达正常水平的CD40L，这表明它们无法帮助B细胞产生Ig是由于其他条件而不是缺乏该分子的表达。最后，外源性IL-2恢复了无能Th2 T细胞对B细胞产生IgE的辅助功能，而IL-4或IL-13的加入大大增强了这一功能。这些数据表明，过敏原来源的肽诱导过敏原特异性Th2 T细胞的能量可能在过敏患者成功脱敏中起重要作用。
The induction of anergy in T cells is believed to be the result of triggering of the TCR in the absence of adequate costimulation mediated through the interaction of CD28 and its ligands, CD80 and CD86. Here, we demonstrate that stimulation of human group I allergen in Dermatophagoides pteronyssinus extract (Der p 1)-specific CD4+ Th2-like T cell clones with Der p 1-derived peptides in the absence of professional APC results in a state of nonresponsiveness. The induction of anergy occurred despite the expression of high levels of CD28, CD80, and CD86 on the surface of the T cell clones and was not prevented by the addition of anti-CD28 mAb. The anergic, Der p 1-specific, Th2 cells failed to mobilize calcium from intracellular stores, to proliferate, and to produce IL-2, IL-4, IL-13, GM-CSF, and TNF-alpha following optimal stimulation with Der p 1-derived peptide and autologous APC. However, they mobilized intracellular calcium following stimulation with Ca(2+)-ionophore and produced all of the above cytokines, including IFN-gamma, when stimulated with phorbol ester and Ca2+ ionophore. These results indicate that the anergic T cell clones are capable of responding to signals circumventing the TCR/CD3 complex activation pathway. In contrast to T cell clones optimally activated with peptide and APC, anergic T cells failed to induce IgG4 and IgE synthesis when cocultured with B cells, even in the presence of exogenous IL-4 or IL-13. Anergic T cells expressed normal levels of CD40L, suggesting that their inability to help in Ig production by B cells is due to conditions other than a lack of expression of this molecule. Finally, exogenous IL-2 restored the helper function of anergic Th2 T cells for IgE production by B cells, which was greatly enhanced by the addition of IL-4 or IL-13. These data suggest that induction of anergy in allergen-specific Th2 T cells by allergen-derived peptides may play an important role in the successful desensitization of allergic patients.