Selective depletion of Foxp3+ Treg during sensitization phase aggravates experimental allergic airway inflammation.
Recent studies highlight the role of Treg in preventing unnecessary responses to allergens and maintaining functional immune tolerance in the lung. We investigated the role of Treg during the sensitization phase in a murine model of experimental allergic airway inflammation by selectively depleting the Treg population in vivo. DEpletion of REGulatory T cells (DEREG) mice were depleted of Treg by diphtheria toxin injection. Allergic airway inflammation was induced using OVA as a model allergen. Pathology was assessed by scoring for differential cellular infiltration in bronchoalveolar lavage, IgE and IgG1 levels in serum, cytokine secretion analysis of lymphocytes from lung draining lymph nodes and lung histology. Use of DEREG mice allowed us for the first time to track and specifically deplete both CD25(+) and CD25(-) Foxp3(+) Treg, and to analyze their significance in limiting pathology in allergic airway inflammation. We observed that depletion of Treg during the priming phase of an active immune response led to a dramatic exacerbation of allergic airway inflammation in mice, suggesting an essential role played by Treg in regulating immune responses against allergens as early as the sensitization phase via maintenance of functional tolerance.
Baru
Abdul Mannan
AM
Institute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research; a joint venture between the Helmholtz Centre for Infection Research (HZI) Braunschweig and the Hannover Medical School (MHH), Germany.
Hartl
Andrea
A
Lahl
Katharina
K
Krishnaswamy
Jayendra Kumar
JK
Fehrenbach
Heinz
H
Yildirim
Ali O
AO
Garn
Holger
H
Renz
Harald
H
Behrens
Georg M N
GM
Sparwasser
Tim
T
D000485:Allergens / Q000008:administration & dosage / Q000276:immunology; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D006967:Hypersensitivity / Q000097:blood / Q000276:immunology* / Q000473:pathology*; D007114:Immunization; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000473:pathology*; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
D000485:Allergens; D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007074:Immunoglobulin G; D007073:Immunoglobulin E; D010047:Ovalbumin