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:  MEDLINE    
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.
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; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-11-14
Journal Detail:
Title:  Mucosal immunology     Volume:  6     ISSN:  1935-3456     ISO Abbreviation:  Mucosal Immunol     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-04-17     Completed Date:  2013-11-13     Revised Date:  2014-11-14    
Medline Journal Info:
Nlm Unique ID:  101299742     Medline TA:  Mucosal Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  580-90     Citation Subset:  IM    
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MeSH Terms
Administration, Intranasal
Adoptive Transfer
Antibodies, Blocking / administration & dosage
Antigens / immunology
Antigens, Differentiation / metabolism
Cells, Cultured
Immune Tolerance*
Lymph Nodes / pathology
Macrophages / immunology*
Membrane Proteins / immunology,  metabolism*
Mice, Inbred BALB C
Ovalbumin / immunology
Phagocytosis / immunology
Respiratory Hypersensitivity / immunology*
T-Lymphocytes / immunology*
Grant Support
P01 AI054456/AI/NIAID NIH HHS; P01 AI054456/AI/NIAID NIH HHS; R01 089955//PHS HHS; R01 AI089955/AI/NIAID NIH HHS
Reg. No./Substance:
0/Antibodies, Blocking; 0/Antigens; 0/Antigens, Differentiation; 0/Membrane Proteins; 0/TIM-4 protein, mouse; 0/monocyte-macrophage differentiation antigen; 9006-59-1/Ovalbumin

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