CD4+CD25+ regulatory T cells reverse established allergic airway inflammation and prevent airway remodeling.
BACKGROUND
CD4(+)CD25(+) regulatory T cells can inhibit excessive T-cell responses in vivo. We have previously demonstrated that prophylactic administration of CD4(+)CD25(+) regulatory T cells suppresses the development of acute allergen-induced airway inflammation in vivo.


OBJECTIVE
We sought to determine the effect of therapeutic transfer of CD4(+)CD25(+) regulatory T cells on established pulmonary inflammation and the subsequent development of airway remodeling.


METHODS
CD4(+)CD25(+) cells were transferred after the onset of allergic inflammation, and airway challenges were continued to induce chronic inflammation and airway remodeling.


RESULTS
Administration of CD4(+)CD25(+) regulatory T cells reduced established lung eosinophilia, T(H)2 infiltration, and expression of IL-5, IL-13, and TGF-beta. Moreover, subsequent mucus hypersecretion and peribronchial collagen deposition were reduced after prolonged challenge. In contrast, transfer of CD4(+)CD25(+) regulatory T cells had no effect on established airway hyperreactivity either 7 days or 4 weeks after transfer.


CONCLUSIONS
In this study we demonstrate for the first time that therapeutic transfer of CD4(+)CD25(+) regulatory T cells can resolve features of chronic allergen-induced inflammation and prevent development of airway remodeling.
Kearley
Jennifer
J
Leukocyte Biology Section, National Heart and Lung Institute, Faculty of Medicine, Imperial College, London, United Kingdom.
Robinson
Douglas S
DS
Lloyd
Clare M
CM
D019264:Adoptive Transfer; D000485:Allergens / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000276:immunology / Q000473:pathology / Q000628:therapy; D002469:Cell Separation; D003094:Collagen / Q000032:analysis; D004804:Eosinophils / Q000276:immunology; D005260:Female; D007073:Immunoglobulin E / Q000097:blood; D007249:Inflammation / Q000276:immunology / Q000473:pathology / Q000628:therapy; D018793:Interleukin-13 / Q000276:immunology / Q000378:metabolism; D015848:Interleukin-5 / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009093:Mucus / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism
D000485:Allergens; D018793:Interleukin-13; D015848:Interleukin-5; D016212:Transforming Growth Factor beta; D007073:Immunoglobulin E; D010047:Ovalbumin; D003094:Collagen