The regulatory T cells induction by epicutaneous immunotherapy is sustained and mediates long-term protection from eosinophilic disorders in peanut-sensitized mice.
The regulatory T cells induction by epicutaneous immunotherapy is sustained and mediates long-term protection from eosinophilic disorders in peanut-sensitized mice.
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DOI：
10.1111/cea.12312
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发表时间：
2014-06
期刊：
影响因子：
--
通讯作者：
Benhamou PH
中科院分区：
文献类型：
--
作者：
Dioszeghy V;Mondoulet L;Dhelft V;Ligouis M;Puteaux E;Dupont C;Benhamou PH
过敏原特异性免疫疗法有利于免疫偏离从Th 2到Th 1反应，并增加调节性T细胞（TcB）的数量。致敏小鼠的表皮免疫疗法（EPIT）降低了临床和变应原特异性Th 2应答，并增加了局部和外周Foxp 3 + T细胞。研究TcR在EPIT中的作用，并描述其表型和EPIT后的维持。使用体内耗竭或过继转移到BALB/c小鼠中来研究T细胞。在EPIT过程中使用抗CD 25抗体注射耗尽TCLs，并将过敏原特异性应答与Sham、单独EPIT和未处理小鼠进行比较。为了证明Tcl 4自身可以介导保护作用，并研究其在EPIT结束后的维持，将从EPIT后不久或8周后的小鼠中分离的CD 25 + CD 4 + Tcl 4转移到花生致敏的小鼠中。将Foxp 3-IRES-mRFP小鼠用EPIT-诱导的TcR转移以分析宿主TcR的诱导。注射抗CD 25抗体可阻断脾脏Tcl 3的诱导和食管Foxp 3的表达。这导致食管中花生诱导的嗜酸性粒细胞浸润水平与假手术相似，并显著高于EPIT。然而，从假手术处理的小鼠转移THBE没有表现出效果，在EPIT后立即转移分离的THBE阻止了花生诱导的嗜酸性粒细胞浸润和嗜酸性粒细胞活化趋化因子表达，并诱导了食管中的Foxp 3。在EPIT后8周分离的TcB的转移与在EPIT后立即分离的TcB一样有效地抑制变应原特异性应答，并且类似地增加脾Foxp 3 + CD 25 + CD 4+细胞。报告小鼠的使用表明宿主TdR增加。这些结果证实了Tregs介导的EPIT机制，并证明了在治疗停止后的很长一段时间内有效的Tregs的持续性。这表明EPIT诱导花生致敏小鼠的长期耐受。
Allergen-specific immunotherapy favours immune deviation from a Th2 to a Th1 response and increases the number of regulatory T cells (Tregs). Epicutaneous immunotherapy (EPIT) of sensitized mice decreases the clinical and the allergen-specific Th2 responses and increases local and peripheral Foxp3+ Tregs. To investigate the role of Tregs in EPIT and characterize their phenotype and maintenance following EPIT. Tregs were investigated using in vivo depletion or adoptive transfer into BALB/c mice. Tregs were depleted using anti-CD25 antibody injection during EPIT, and allergen-specific responses were compared with Sham, EPIT alone and naïve mice. To demonstrate that Tregs can mediate protection by their own, and to study their maintenance following the end of EPIT, CD25+CD4+ Tregs isolated from mice just after or 8 weeks after EPIT were transferred into peanut-sensitized mice. Foxp3-IRES-mRFP mice were transferred with EPIT-induced Tregs to analyse the induction of host Tregs. The anti-CD25 antibody injection to EPIT mice abrogated the induction of Tregs in spleen and the expression of Foxp3 in oesophagus. This resulted in levels of peanut-induced eosinophilic infiltration in oesophagus similar to Sham and significantly higher than EPIT. Whereas the transfer of Tregs from Sham-treated mice demonstrated no effect, the transfer of Tregs isolated just after EPIT prevented peanut-induced eosinophil infiltration and eotaxin expression and induced Foxp3 in oesophagus. The transfer of Tregs isolated 8 weeks after EPIT suppressed allergen-specific responses as efficiently as did Tregs isolated just after EPIT and increased spleen Foxp3+ CD25+ CD4+ cells similarly. The use of reporter mice demonstrated an increase in host Tregs. These results confirm the Tregs-mediated mechanism of EPIT and demonstrate the persistence of efficient Tregs during a long period of time after treatment cessation. This suggests that EPIT induces long-term tolerance in peanut-sensitized mice.
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影响因子：
15.3
作者：
Karlsson, MR;Rugtveit, J;Brandtzaeg, P
通讯作者：
Brandtzaeg, P
影响因子：
14.2
作者：
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作者：
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作者：
Dioszeghy, Vincent;Mondoulet, Lucie;Dupont, Christophe
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