title: T(H)17 cells mediate pulmonary collateral priming.
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.
authors: Junior Research Group SFB 587, Medical School Hannover, Hannover, Germany.
authors: Melanie
authors: M
authors: Albrecht
authors: Hui-Chen
authors: HC
authors: Chen
authors: Paula
authors: P
authors: Preston-Hurlburt
authors: Patricia
authors: P
authors: Ranney
authors: Heinz-Gerd
authors: HG
authors: Hoymann
authors: Joachim
authors: J
authors: Maxeiner
authors: Valérie
authors: V
authors: Staudt
authors: Christian
authors: C
authors: Taube
authors: H Kim
authors: HK
authors: Bottomly
authors: Anna-Maria
authors: AM
authors: Dittrich
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002469:Cell Separation; D005434:Flow Cytometry; D001239:Inhalation; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D011014:Pneumonia / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D020381:Interleukin-17