Document Detail


Tolerance induction by intrathymic inoculation prevents chronic renal allograft rejection.
MedLine Citation:
PMID:  9458029     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: These experiments investigated the ability of the donor-specific unresponsiveness created by the intrathymic inoculation of donor alloantigen to effectively prevent chronic rejection in an established rat model of chronic renal allograft rejection. METHODS: Three study groups were examined: (1) Allograft controls--F-344 rats received a Lewis renal allograft plus 10 days of low-dose cyclosporine (CsA); (2) isograft controls--F-344 rats received an F-344 renal isograft and low-dose CsA; (3) experimental group--F-344 rats received a T-cell depleted syngeneic bone marrow transplant and intrathymic injection of Lewis bone marrow. Twenty-one days after bone marrow transplant, these animals received a Lewis renal allograft. RESULTS: Allograft controls demonstrated severe parenchymal fibrosis; isograft controls and intrathymic (IT) animals failed to develop this lesion. Immunohistochemical analysis revealed increased CD4+ T cells infiltrating the cortex of the allograft controls. Cytokine interferon-gamma and interleukin-2 transcripts were strongly positive in allograft controls and were absent from isograft controls and IT allografts as determined by reverse transcriptase-polymerase chain reaction. Analysis of tolerant grafts by flow microfluorimetry and genomic DNA amplification could not detect chimerism to a level of < 0.1%. CONCLUSION: IT inoculation of donor alloantigen can confer long-term unresponsiveness and prevent the development of the characteristic lesions of chronic rejection.
Authors:
D Blom; N Morrissey; C Mesonero; X J Zuo; S Jordan; T Fisher; O Bronsther; M S Orloff
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Transplantation     Volume:  65     ISSN:  0041-1337     ISO Abbreviation:  Transplantation     Publication Date:  1998 Jan 
Date Detail:
Created Date:  1998-02-11     Completed Date:  1998-02-11     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0132144     Medline TA:  Transplantation     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  272-5     Citation Subset:  IM    
Affiliation:
Department of Surgery, University of Rochester School of Medicine and Dentistry, New York 14642, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Bone Marrow Transplantation / immunology*
Graft Rejection / prevention & control*
Immune Tolerance*
Injections
Isoantigens / administration & dosage,  pharmacology*,  therapeutic use
Kidney Transplantation / immunology*,  pathology
Lymphocyte Depletion
Rats
Rats, Inbred F344
Rats, Inbred Lew
Thymus Gland
Transplantation Chimera*
Transplantation, Homologous
Grant Support
ID/Acronym/Agency:
5R29-AI33054-03/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Isoantigens

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


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