M C Liu1, H Q Xiao1, L M Breslin1, B S Bochner2, J T Schroeder1. 1. School of Medicine, Johns Hopkins University, Baltimore, MD, USA. 2. Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Abstract
BACKGROUND: Allergic inflammation is a common feature of asthma and may contribute to both development and perpetuation of disease. The interaction of antigen-presenting cells (APC) with sensitized helper T lymphocytes (TC) producing Th2 cytokines may determine the inflammatory response. Recruitment of APC and TC to the lung during allergic responses has been demonstrated, but functional studies in humans have been limited. OBJECTIVE: This study examined the function of APC and TC accumulating at sites of inflammation after segmental allergen challenge (SAC). METHODS: Fifteen allergic patients underwent SAC, and cells from bronchoalveolar lavage (BAL) were collected after 24 hours. APC and TC from the blood and BAL were purified based on expression of the monocyte marker, CD14; the plasmacytoid dendritic cell (pDC) marker, BDCA4, identifying neuropilin-1 (NRP1); and the helper T cell marker, CD4. Functional activity was assessed using allergen-induced T cell proliferation. Flow cytometry identified cells expressing CD14 and NRP1. RESULTS: SAC resulted in a 12-fold increase in mononuclear cells having the morphologic appearance of blood monocytes. Most of these cells co-expressed CD14 and NRP1. After saline challenge, BAL mononuclear cells demonstrated little APC function. Following SAC, BAL mononuclear cells showed function equal to pDC from blood and greater than blood monocytes. Purified NRP1+ cells from BAL had even greater function than pDC cells from blood (P = .008). Using consistent sources of APC, enhanced proliferation of TC from lung compared to blood was also demonstrated (P = .002). CONCLUSIONS: The marked increase in APC function for allergen-specific TC proliferation during allergic inflammation is largely due to the recruitment of monocytes and dendritic cells. There is also an enhanced response in the lung TC population, consistent with recruitment of allergen-specific T cells. Interactions between recruited APC and TC may occur as an early event promoting allergic airway inflammation.
BACKGROUND:Allergic inflammation is a common feature of asthma and may contribute to both development and perpetuation of disease. The interaction of antigen-presenting cells (APC) with sensitized helper T lymphocytes (TC) producing Th2 cytokines may determine the inflammatory response. Recruitment of APC and TC to the lung during allergic responses has been demonstrated, but functional studies in humans have been limited. OBJECTIVE: This study examined the function of APC and TC accumulating at sites of inflammation after segmental allergen challenge (SAC). METHODS: Fifteen allergic patients underwent SAC, and cells from bronchoalveolar lavage (BAL) were collected after 24 hours. APC and TC from the blood and BAL were purified based on expression of the monocyte marker, CD14; the plasmacytoid dendritic cell (pDC) marker, BDCA4, identifying neuropilin-1 (NRP1); and the helper T cell marker, CD4. Functional activity was assessed using allergen-induced T cell proliferation. Flow cytometry identified cells expressing CD14 and NRP1. RESULTS: SAC resulted in a 12-fold increase in mononuclear cells having the morphologic appearance of blood monocytes. Most of these cells co-expressed CD14 and NRP1. After saline challenge, BAL mononuclear cells demonstrated little APC function. Following SAC, BAL mononuclear cells showed function equal to pDC from blood and greater than blood monocytes. Purified NRP1+ cells from BAL had even greater function than pDC cells from blood (P = .008). Using consistent sources of APC, enhanced proliferation of TC from lung compared to blood was also demonstrated (P = .002). CONCLUSIONS: The marked increase in APC function for allergen-specific TC proliferation during allergic inflammation is largely due to the recruitment of monocytes and dendritic cells. There is also an enhanced response in the lung TC population, consistent with recruitment of allergen-specific T cells. Interactions between recruited APC and TC may occur as an early event promoting allergic airway inflammation.
Authors: Nicolas Regamey; Carolina Obregon; Sylvie Ferrari-Lacraz; Coretta van Leer; Marc Chanson; Laurent P Nicod; Thomas Geiser Journal: Am J Respir Cell Mol Biol Date: 2007-03-15 Impact factor: 6.914
Authors: N P O'Grady; H L Preas; J Pugin; C Fiuza; M Tropea; D Reda; S M Banks; A F Suffredini Journal: Am J Respir Crit Care Med Date: 2001-06 Impact factor: 21.405
Authors: S J Till; S R Durham; K Rajakulasingam; M Humbert; D Huston; R Dickason; A B Kay; C J Corrigan Journal: Am J Respir Crit Care Med Date: 1998-08 Impact factor: 21.405
Authors: Roshi Afshar; James P Strassner; Edward Seung; Benjamin Causton; Josalyn L Cho; R Scott Harris; Daniel L Hamilos; Benjamin D Medoff; Andrew D Luster Journal: J Allergy Clin Immunol Date: 2013-04-28 Impact factor: 10.793
Authors: Mirjam Kool; Menno van Nimwegen; Monique A M Willart; Femke Muskens; Louis Boon; Joost J Smit; Anthony Coyle; Björn E Clausen; Henk C Hoogsteden; Bart N Lambrecht; Hamida Hammad Journal: J Immunol Date: 2009-06-24 Impact factor: 5.422
Authors: A Nicole Desch; Sophie L Gibbings; Rajni Goyal; Raivo Kolde; Joe Bednarek; Tullia Bruno; Jill E Slansky; Jordan Jacobelli; Robert Mason; Yoko Ito; Elise Messier; Gwendalyn J Randolph; Miglena Prabagar; Shaikh M Atif; Elodie Segura; Ramnik J Xavier; Donna L Bratton; William J Janssen; Peter M Henson; Claudia V Jakubzick Journal: Am J Respir Crit Care Med Date: 2016-03-15 Impact factor: 21.405
Authors: Joong C Huh; Deborah H Strickland; Frode L Jahnsen; Debra J Turner; Jenny A Thomas; Sylvia Napoli; Iriani Tobagus; Philip A Stumbles; Peter D Sly; Patrick G Holt Journal: J Exp Med Date: 2003-06-30 Impact factor: 14.307