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T(H)17 cells mediate pulmonary collateral priming

 
: Albrecht, Melanie; Chen, Hui-Chen; Preston-Hurlburt, Paula; Ranney, Patricia; Hoymann, Heinz-Gerd; Maxeiner, Joachim; Staudt, Valérie; Taube, Christian; Bottomly, H. Kim; Dittrich, Anna-Maria

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The journal of allergy and clinical immunology : JACI 128 (2011), Nr.1, S.168-177.e8
ISSN: 0091-6749
ISSN: 1097-6825
ISSN: 1085-8725
Englisch
Zeitschriftenaufsatz
Fraunhofer ITEM ()
IL-17A; TH cell; polysensitization; asthma

Abstract
BACKGROUND:
Our laboratory has shown that inhalational sensitization to new antigens is facilitated through an ongoing T(H)2-polarized inflammation of the lung, a phenomenon we call "collateral priming."
OBJECTIVE:
We were interested to analyze whether a T(H)1-polarized pulmonary inflammation also facilitates priming toward new antigens and which cytokine or cytokines are involved.
METHODS:
T(H)1-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(H)1 collateral priming.
RESULTS:
Our experiments revealed that ongoing inflammation of the lung induced by the transfer of T(H)1-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(H)17-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(H)1 cells, thus presenting an exciting model to further elucidate differentiation of T(H)17 cells.
CONCLUSIONS:
We show that airway inflammation mediated by T(H)17 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.

: http://publica.fraunhofer.de/dokumente/N-191157.html