Document Detail


Reperfusion injury intensifies the adaptive human T cell alloresponse in a human-mouse chimeric artery model.
MedLine Citation:
PMID:  22053072     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Perioperative nonimmune injuries to an allograft can decrease graft survival. We have developed a model for studying this process using human materials.
METHODS AND RESULTS: Human artery segments were transplanted as infrarenal aortic interposition grafts into an immunodeficient mouse host, allowed to "heal in" for 30 days, and then retransplanted into a second mouse host. To induce a reperfusion injury, the healed-in artery segments were incubated for 3 hours under hypoxic conditions ex vivo before retransplantation. To induce immunologic rejection, the animals receiving the retransplanted artery segment were adoptively transferred with human peripheral blood mononuclear cells or purified T cells from a donor allogeneic to the artery 1 week before surgery. To compare rejection of injured versus healthy tissues, these manipulations were combined. Results were analyzed ex vivo by histology, morphometry, immunohistochemistry, and mRNA quantitation or in vivo by ultrasound. Our results showed that reperfusion injury, which otherwise heals with minimal sequelae, intensifies the degree of allogeneic T cell-mediated injury to human artery segments.
CONCLUSIONS: We developed a new human-mouse chimeric model demonstrating interactions of reperfusion injury and alloimmunity using human cells and tissues that may be adapted to study other forms of nonimmune injury and other types of adaptive immune responses.
Authors:
Tai Yi; Birgit Fogal; Zhengrong Hao; Zuzana Tobiasova; Chen Wang; Deepak A Rao; Rafia S Al-Lamki; Nancy C Kirkiles-Smith; Sanjay Kulkarni; John R Bradley; Alfred L M Bothwell; William C Sessa; George Tellides; Jordan S Pober
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-11-03
Journal Detail:
Title:  Arteriosclerosis, thrombosis, and vascular biology     Volume:  32     ISSN:  1524-4636     ISO Abbreviation:  Arterioscler. Thromb. Vasc. Biol.     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-01-19     Completed Date:  2012-03-13     Revised Date:  2014-04-25    
Medline Journal Info:
Nlm Unique ID:  9505803     Medline TA:  Arterioscler Thromb Vasc Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  353-60     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adaptive Immunity / physiology*
Adult
Animals
Arteries / immunology*,  pathology,  transplantation*
Chimera / immunology*
Graft Rejection / immunology,  physiopathology
Graft Survival / immunology,  physiology
Humans
Mice
Mice, SCID
Models, Animal
Reperfusion Injury / physiopathology*
T-Lymphocytes / immunology*,  pathology
Transplantation, Homologous
Grant Support
ID/Acronym/Agency:
P01 HL070295-10/HL/NHLBI NIH HHS; P01-HL070295/HL/NHLBI NIH HHS; R01 HL109455-01/HL/NHLBI NIH HHS; R01-HL109455/HL/NHLBI NIH HHS; T32 GM007205/GM/NIGMS NIH HHS; T32-GM07205/GM/NIGMS NIH HHS; T32-HL007950/HL/NHLBI NIH HHS
Comments/Corrections
Comment In:
Arterioscler Thromb Vasc Biol. 2012 Feb;32(2):163-4   [PMID:  22258896 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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