| LFA-1 antagonism inhibits early infiltration of endogenous memory CD8 T cells into cardiac allografts and donor-reactive T cell priming. | |
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MedLine Citation:
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PMID: 21466654 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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K Setoguchi; A D Schenk; D Ishii; Y Hattori; W M Baldwin; K Tanabe; R L Fairchild |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-04-05 |
Journal Detail:
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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:
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Created Date: 2011-04-27 Completed Date: 2011-10-17 Revised Date: 2011-11-21 |
Medline Journal Info:
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Nlm Unique ID: 100968638 Medline TA: Am J Transplant Country: United States |
Other Details:
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Languages: eng Pagination: 923-35 Citation Subset: IM |
Copyright Information:
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©2011 The Authors Journal compilation©2011 The American Society of Transplantation and the American Society of Transplant Surgeons. |
Affiliation:
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Glickman Urological and Kidney Institute Department of Immunology, Cleveland Clinic Foundation, Cleveland, OH, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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:
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R01 AI040459-15/AI/NIAID NIH HHS; R01 AI40459/AI/NIAID NIH HHS; R01 AI74740/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antibodies, Monoclonal; 0/Lymphocyte Function-Associated Antigen-1; 0/anti-LFA-1 monoclonal antibody |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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