CD4+ cells are required for chronic eosinophilic lung inflammation but not airway remodeling.
The contribution of CD4 T cells and other CD4+ cells to lung inflammation and airway remodeling remains unclear during bouts of chronic exposure to airborne allergen. Previously, murine models have shown that CD4 T cells are required for initiation of acute inflammation and the remodeling process. However, it is unknown whether CD4 T cells or other CD4+ cells continue to be required for remodeling during ongoing allergen challenges after the development of acute eosinophilic lung inflammation. To test this, mice were sensitized and challenged with ovalbumin (OVA). After acute airway inflammation was established, a CD4 depleting antibody was administered for 4 wk during a period of chronic exposure to intranasal OVA, resulting in effective depletion of CD4+ cells from all organs, including the lung, lung-draining lymph nodes, and spleen. In these mice, levels of peribronchial inflammation, bronchoalveolar (BAL) eosinophils, and lung CD11c+, CD8+, and Siglec-F+CD11c- cells were significantly reduced. However, mucus metaplasia, peribronchial subepithelial fibrosis, and smooth muscle mass were not affected. Additionally, depletion of CD4+ cells before the last week of chronic allergen challenges also led to significant reductions in BAL eosinophils, peribronchial inflammation, and lung CD11c+, CD8+, and Siglec-F+CD11c- cells. These results show that CD4 T cells, and other CD4+ cells including subsets of dendritic cells, iNKT cells, and LTi cells, play a role in ongoing eosinophilic lung inflammation during periods of chronic allergen challenge, but are not required for progressive airway remodeling that develops after initial acute inflammation.
Doherty
Taylor A
TA
La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
Soroosh
Pejman
P
Broide
David H
DH
Croft
Michael
M
D000485:Allergens / Q000276:immunology / Q000378:metabolism; D000818:Animals; D001249:Asthma / Q000276:immunology*; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002908:Chronic Disease; D058544:Class Ib Phosphatidylinositol 3-Kinase; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D015151:Immunoblotting; D007527:Isoenzymes / Q000502:physiology; D008168:Lung / Q000276:immunology / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D055611:Natural Killer T-Cells / Q000276:immunology / Q000378:metabolism; D010047:Ovalbumin / Q000008:administration & dosage; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D011657:Pulmonary Eosinophilia / Q000276:immunology*; D012137:Respiratory System / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
D000485:Allergens; D007527:Isoenzymes; D010047:Ovalbumin; D019869:Phosphatidylinositol 3-Kinases; D058544:Class Ib Phosphatidylinositol 3-Kinase; C546764:Pik3cg protein, mouse