Document Detail

TIM-4, expressed by medullary macrophages, regulates respiratory tolerance by mediating phagocytosis of antigen-specific T cells.
MedLine Citation:
PMID:  23149665     Owner:  NLM     Status:  Publisher    
Respiratory exposure to antigen induces T cell tolerance via several overlapping mechanisms that limit the immune response. While the mechanisms involved in the development of Treg cells have received much attention, those that result in T cell deletion are largely unknown. Herein, we show that F4/80(+) lymph node medullary macrophages expressing TIM-4, a phosphatidylserine receptor, remove antigen-specific T cells during respiratory tolerance, thereby reducing secondary T cell responses. Blockade of TIM-4 inhibited the phagocytosis of antigen-specific T cells by TIM-4 expressing lymph node medullary macrophages, resulting in an increase in the number of antigen-specific T cells and the abrogation of respiratory tolerance. Moreover, specific depletion of medullary macrophages inhibited the induction of respiratory tolerance, highlighting the key role of TIM-4 and medullary macrophages in tolerance. Therefore, TIM-4-mediated clearance of antigen specific T cells represents an important previously unrecognized mechanism regulating respiratory tolerance.Mucosal Immunology advance online publication 14 November 2012; doi:10.1038/mi.2012.100.
L A Albacker; S Yu; D Bedoret; W-L Lee; S E Umetsu; S Monahan; G J Freeman; D T Umetsu; R H Dekruyff
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-14
Journal Detail:
Title:  Mucosal immunology     Volume:  -     ISSN:  1935-3456     ISO Abbreviation:  Mucosal Immunol     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101299742     Medline TA:  Mucosal Immunol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Division of Immunology, Children's Hospital Boston, and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA.
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