T cell suppression in transplantation tolerance through linked recognition.

Allogeneic tissues transplanted to mice treated with CD4- and CD8-specific Abs are often accepted indefinitely due to the induction of immunologic tolerance. When transplantation tolerance was induced to grafts mismatched at multiple minor histocompatibility loci, Ag specificity was inferred because...

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Main Authors: Davies, J, Leong, L, Mellor, A, Cobbold, S, Waldmann, H
Format: Journal article
Language:English
Published: 1996
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author Davies, J
Leong, L
Mellor, A
Cobbold, S
Waldmann, H
author_facet Davies, J
Leong, L
Mellor, A
Cobbold, S
Waldmann, H
author_sort Davies, J
collection OXFORD
description Allogeneic tissues transplanted to mice treated with CD4- and CD8-specific Abs are often accepted indefinitely due to the induction of immunologic tolerance. When transplantation tolerance was induced to grafts mismatched at multiple minor histocompatibility loci, Ag specificity was inferred because third party grafts, mismatched at the MHC, were rejected normally. However, some "third party" grafts were either accepted, or rejected more slowly. Tolerant mice possess CD4+ cells, which suppress rejection by T cells reacting to the same grafts. Therefore, we hypothesized that tolerated third party grafts might share Ags with the original tolerizing graft, and that these Ags are a target for such suppression. To test this idea, we tolerized mice to a set of minor Ags (B10 minors) and challenged them with third party grafts that carried those minors, as well as an additional strong transplantation Ag, the class I MHC molecule, H-2Kb. This class I molecule acts as a good target for rejection in both naive mice and in mice tolerized to B10 minors. However, when this third party class I molecule is provided "linked" to those B10 minors on an F1 graft, rejection was significantly impaired. The data suggest that suppression within tolerant animals operates locally (perhaps on the same APC) via linked recognition. In addition, our preliminary findings suggest that suppression via linked recognition can also lead to tolerance to the third party Ag.
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spelling oxford-uuid:9a3a09bd-389c-4e2d-ba09-38a2cfed74b52022-03-27T00:19:51ZT cell suppression in transplantation tolerance through linked recognition.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:9a3a09bd-389c-4e2d-ba09-38a2cfed74b5EnglishSymplectic Elements at Oxford1996Davies, JLeong, LMellor, ACobbold, SWaldmann, HAllogeneic tissues transplanted to mice treated with CD4- and CD8-specific Abs are often accepted indefinitely due to the induction of immunologic tolerance. When transplantation tolerance was induced to grafts mismatched at multiple minor histocompatibility loci, Ag specificity was inferred because third party grafts, mismatched at the MHC, were rejected normally. However, some "third party" grafts were either accepted, or rejected more slowly. Tolerant mice possess CD4+ cells, which suppress rejection by T cells reacting to the same grafts. Therefore, we hypothesized that tolerated third party grafts might share Ags with the original tolerizing graft, and that these Ags are a target for such suppression. To test this idea, we tolerized mice to a set of minor Ags (B10 minors) and challenged them with third party grafts that carried those minors, as well as an additional strong transplantation Ag, the class I MHC molecule, H-2Kb. This class I molecule acts as a good target for rejection in both naive mice and in mice tolerized to B10 minors. However, when this third party class I molecule is provided "linked" to those B10 minors on an F1 graft, rejection was significantly impaired. The data suggest that suppression within tolerant animals operates locally (perhaps on the same APC) via linked recognition. In addition, our preliminary findings suggest that suppression via linked recognition can also lead to tolerance to the third party Ag.
spellingShingle Davies, J
Leong, L
Mellor, A
Cobbold, S
Waldmann, H
T cell suppression in transplantation tolerance through linked recognition.
title T cell suppression in transplantation tolerance through linked recognition.
title_full T cell suppression in transplantation tolerance through linked recognition.
title_fullStr T cell suppression in transplantation tolerance through linked recognition.
title_full_unstemmed T cell suppression in transplantation tolerance through linked recognition.
title_short T cell suppression in transplantation tolerance through linked recognition.
title_sort t cell suppression in transplantation tolerance through linked recognition
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AT leongl tcellsuppressionintransplantationtolerancethroughlinkedrecognition
AT mellora tcellsuppressionintransplantationtolerancethroughlinkedrecognition
AT cobbolds tcellsuppressionintransplantationtolerancethroughlinkedrecognition
AT waldmannh tcellsuppressionintransplantationtolerancethroughlinkedrecognition