TH 17 cells mediate pulmonary collateral priming

• Published in: Journal of allergy and clinical immunology 2011, Vol.128 (1), p.168-177.e8
• Main Authors: Albrecht, Melanie, PhD, Chen, Hui-Chen, PhD, Preston-Hurlburt, Paula, Ranney, Patricia, Hoymann, Heinz-Gerd, PhD, Maxeiner, Joachim, PhD, Staudt, Valérie, MS, Taube, Christian, MD, Bottomly, H. Kim, PhD, Dittrich, Anna-Maria, MD
• Format: Article
• Language: English
• Subjects: Allergy and Immunology
• ISSN: 0091-6749
• DOI: 10.1016/j.jaci.2011.01.067

Background Our laboratory has shown that inhalational sensitization to new antigens is facilitated through an ongoing TH 2-polarized inflammation of the lung, a phenomenon we call “collateral priming.” Objective We were interested to analyze whether a TH 1-polarized pulmonary inflammation also facilitates priming toward new antigens and which cytokine or cytokines are involved. Methods TH 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 TH 1 collateral priming. Results Our experiments revealed that ongoing inflammation of the lung induced by the transfer of TH 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 TH 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 TH 1 cells, thus presenting an exciting model to further elucidate differentiation of TH 17 cells. Conclusions We show that airway inflammation mediated by TH 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.