T_H17 cells mediate pulmonary collateral priming

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• 作者：Melanie Albrecht PhD^a ; Hui-Chen Chen PhD^b ; ^c ; Paula Preston-Hurlburt^b ; Patricia Ranney^b ; Heinz-Gerd Hoymann PhD^d ; Joachim Maxeiner PhD^e ; Valé ; rie Staudt MS^f ; Christian Taube MD^e ; H. Kim Bottomly PhD^b ; ^g ; Anna-Maria Dittrich MD^a ; ^{dittrich.anna-maria@mh-hannover.de"" rel=""nofollow}
• 关键词：Asthma ; IL-17A ; T_H cell ; polysensitization
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2011
• 出版时间：July 2011
• 年：2011
• 卷：128
• 期：1
• 页码：168-177.e8
• 全文大小：1966 K

文摘

Background

Our laboratory has shown that inhalational sensitization to new antigens is facilitated through an ongoing T_H2-polarized inflammation of the lung, a phenomenon we call “collateral priming.”

Objective

We were interested to analyze whether a T_H1-polarized pulmonary inflammation also facilitates priming toward new antigens and which cytokine or cytokines are involved.

Methods

T_H1-polarized T cells were generated in vitro and transferred into congenic mice. Mice were challenged initially with cognate antigen and an unrelated antigen; consecutively, they received cognate antigen or the secondary antigen. Airway inflammation, antigen-specific IgG2a levels, and airway hyperresponsiveness were assessed to determine the inflammatory phenotype, with antibody blocking studies used to determine cytokine requirements for T_H1 collateral priming.

Results

Our experiments revealed that ongoing inflammation of the lung induced by the transfer of T_H1-polarized cells also facilitates priming toward new antigens, which results in lymphocytic inflammation of the lung. Interestingly, blocking studies identified IL-17A as a major contributor to this pathology. Accordingly, we could demonstrate for the first time that T_H17-polarized cells alone can facilitate priming toward new antigens, inducing lymphocytic airway inflammation and strong airway hyperresponsiveness. Flow cytometric analysis revealed priming of endogenous T cells for IL-17A secretion with a distinct memory/effector phenotype compared to T_H1 cells, thus presenting an exciting model to further elucidate differentiation of T_H17 cells.

Conclusions

We show that airway inflammation mediated by T_H17 cells facilitates sensitization to new antigens and confers increased airway responsiveness in a murine model of polysensitization, suggesting a mechanism involving IL-17A behind the increased risk for allergic sensitization in polysensitized subjects.