Document Detail


T regulatory cells play a significant role in modulating MHC class I antibody-induced obliterative airway disease.
MedLine Citation:
PMID:  22822907     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The molecular mechanisms leading to the development of chronic lung allograft dysfunction following de novo development of antibodies to mismatched donor MHC remain undefined. We demonstrated that intrabronchial administration of antibodies to MHC class I resulted in induction of both innate and adaptive cellular immune responses characterized by a predominance of Th17 specific to lung associated self-antigens Kα1-tubulin and Collagen-V leading to the development of obliterative airway lesions (OAD), correlate of chronic rejection following human lung transplantation. To determine the role of regulatory T cells (Treg) in the pathogenesis of OAD, we administered anti-MHC class I to mice, in which Treg were depleted by conditional ablation of FoxP3+cells. Under this condition, we observed a threefold increase in pulmonary cellular infiltration, luminal occlusion and fibrous deposition when compared anti-MHC class I Ab administered mice maintaining FoxP3. OAD lesions were accompanied with enhanced accumulation of neutrophils along with self-antigen-specific Th17 and humoral responses. However, IL-17-blockade or adoptive transfer of Treg abrogated OAD. We conclude that Treg exerts a suppressive effect on anti-MHC induced IL-8-mediated neutrophil infiltration and innate immune responses that leads to inhibition of Th17 immune responses to lung associated self-antigens which is critical for development of OAD.
Authors:
V Tiriveedhi; M Takenaka; S Ramachandran; A E Gelman; V Subramanian; G A Patterson; T Mohanakumar
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-07-23
Journal Detail:
Title:  American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons     Volume:  12     ISSN:  1600-6143     ISO Abbreviation:  Am. J. Transplant.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-09-26     Completed Date:  2013-02-25     Revised Date:  2013-10-17    
Medline Journal Info:
Nlm Unique ID:  100968638     Medline TA:  Am J Transplant     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2663-74     Citation Subset:  IM    
Copyright Information:
© Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.
Affiliation:
Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA.
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MeSH Terms
Descriptor/Qualifier:
Adoptive Transfer
Animals
Autoantibodies / immunology*
Bronchiolitis Obliterans / immunology*
Histocompatibility Antigens Class I / immunology*
Immunity, Cellular
Immunity, Innate
Interleukin-17 / immunology
Mice
T-Lymphocytes, Regulatory / immunology*
Grant Support
ID/Acronym/Agency:
HL092514-01A2/HL/NHLBI NIH HHS; R01 HL092514/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Autoantibodies; 0/Histocompatibility Antigens Class I; 0/Interleukin-17
Comments/Corrections

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