Document Detail


LFA-1 antagonism inhibits early infiltration of endogenous memory CD8 T cells into cardiac allografts and donor-reactive T cell priming.
MedLine Citation:
PMID:  21466654     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Alloreactive memory T cells are present in virtually all transplant recipients due to prior sensitization or heterologous immunity and mediate injury undermining graft outcome. In mouse models, endogenous memory CD8 T cells infiltrate MHC-mismatched cardiac allografts and produce IFN-γ in response to donor class I MHC within 24 h posttransplant. The current studies analyzed the efficacy of anti-LFA-1 mAb to inhibit early CD8 T cell cardiac allograft infiltration and activation. Anti-LFA-1 mAb given to C57BL/6 6 (H-2(b)) recipients of A/J (H-2(a)) heart grafts on days -1 and 0 completely inhibited CD8 T cell allograft infiltration, markedly decreased neutrophil infiltration and significantly reduced intragraft expression levels of IFN-γ-induced genes. Donor-specific T cells producing IFN-γ were at low/undetectable numbers in spleens of anti-LFA-1 mAb treated recipients until day 21. These effects combined to promote substantial prolongation (from day 8 to 27) in allograft survival. Delaying anti-LFA-1 mAb treatment until days 3 and 4 posttransplant did not inhibit early memory CD8 T cell infiltration and proliferation within the allograft. These data indicate that peritransplant anti-LFA-1 mAb inhibits early donor-reactive memory CD8 T cell allograft infiltration and inflammation suggesting an effective strategy to attenuate the negative effects of heterologous immunity in transplant recipients.
Authors:
K Setoguchi; A D Schenk; D Ishii; Y Hattori; W M Baldwin; K Tanabe; R L Fairchild
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-04-05
Journal Detail:
Title:  American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons     Volume:  11     ISSN:  1600-6143     ISO Abbreviation:  Am. J. Transplant.     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-04-27     Completed Date:  2011-10-17     Revised Date:  2014-11-09    
Medline Journal Info:
Nlm Unique ID:  100968638     Medline TA:  Am J Transplant     Country:  United States    
Other Details:
Languages:  eng     Pagination:  923-35     Citation Subset:  IM    
Copyright Information:
©2011 The Authors Journal compilation©2011 The American Society of Transplantation and the American Society of Transplant Surgeons.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies, Monoclonal / metabolism,  therapeutic use*
CD8-Positive T-Lymphocytes / cytology,  immunology*
Flow Cytometry / methods
Heart Transplantation / methods*
Immunohistochemistry / methods
Immunologic Memory
Lymphocyte Function-Associated Antigen-1 / metabolism*
Male
Mice
Mice, Inbred C57BL
Reverse Transcriptase Polymerase Chain Reaction
T-Lymphocytes / cytology*
Transplantation, Homologous / methods
Grant Support
ID/Acronym/Agency:
R01 AI040459/AI/NIAID NIH HHS; R01 AI040459-15/AI/NIAID NIH HHS; R01 AI40459/AI/NIAID NIH HHS; R01 AI74740/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Lymphocyte Function-Associated Antigen-1; 0/anti-LFA-1 monoclonal antibody
Comments/Corrections

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


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