Achieving permanent survival of islet xenografts by independent manipulation of direct and indirect T-cell responses

Détails

ID Serval
serval:BIB_AD99D0A3A92E
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Achieving permanent survival of islet xenografts by independent manipulation of direct and indirect T-cell responses
Périodique
Diabetes
Auteur(s)
Mirenda  V., Golshayan  D., Read  J., Berton  I., Warrens  A. N., Dorling  A., Lechler  R. I.
ISSN
0012-1797 (Print)
Statut éditorial
Publié
Date de publication
04/2005
Volume
54
Numéro
4
Pages
1048-55
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Apr
Résumé
Recent success in pancreatic islet allotransplantation has raised expectations but has equally highlighted the acute shortage of donor tissue. The use of xenogeneic tissue would help to address this shortage; however, strong cellular immunity limits the application of this approach. T-cell responses to xenogeneic tissues involve recognition of intact species-mismatched major histocompatibility complex (MHC) molecules, the direct pathway, and xenogeneic proteins presented as peptides by responder-type MHC molecules, the indirect pathway. In this study, we exploited the species difference to selectively and sequentially inhibit direct and indirect xenoresponses after transplantation of porcine islets into mice. Selective inhibition of the direct response was achieved using porcine CTLA4-Ig, which binds preferentially to pig versus mouse B7 molecules. Selective inhibition of the indirect response was achieved using murine CTLA4-Ig, which binds preferentially to mouse B7 molecules. Administration of porcine CTLA4-Ig alone caused modest prolongation of islet survival. Injection of murine CTLA4-Ig alone had a minimal effect. However, the injection of the porcine fusion protein early and the murine homolog late after grafting led to permanent survival of the porcine islets, in the absence of any other immunosuppression. These results suggest that a similar approach could have clinical utility in porcine islet xenotransplantation.
Mots-clé
Animals Antigen-Antibody Reactions Genes, MHC Class II/genetics/immunology Graft Rejection/*prevention & control Immunoconjugates/immunology Islets of Langerhans Transplantation/*immunology Lymphocyte Activation/*immunology Male Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Swine T-Lymphocytes/*immunology Transplantation, Heterologous
Pubmed
Web of science
Open Access
Oui
Création de la notice
25/01/2008 14:45
Dernière modification de la notice
20/08/2019 16:17
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