Titre
Viral peptide specific cytotoxic T lymphocytes are of high avidity to host-MHC but only low avidity to donor-MHC after allogeneic bone marrow transplantation
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Kyburz, D.
Auteure/Auteur
Speiser, D. E.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
0966-3274
Statut éditorial
Publié
Date de publication
1995-06
Volume
3
Numéro
2
Première page
143
Dernière page/numéro d’article
50
Notes
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S. --- Old month value: Jun
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S. --- Old month value: Jun
Résumé
In the thymus maturing T lymphocytes are positively selected for efficient interaction with self-MHC molecules. Consequently, mature peripheral T cells recognize foreign (microbial) antigens in association with self-MHC molecules (known as MHC restricted recognition). In experimental bone marrow transplantation (BMT) lymphohaemopoietic stem cells from an MHC disparate donor transfused to an irradiated host give rise to mature T lymphocytes with host-MHC restriction specificity. While experiments with T cell receptor transgenic mice have largely confirmed this concept, many studies using genetically unmanipulated animals analysing polyclonal T cell repertoires have also shown donor-MHC restricted T cell activities after allogeneic BMT. To analyse this discrepancy we generated 18 virus specific cytotoxic T cell (CTL) clones, 16 from F1 into parent and two from fully allogeneic bone marrow chimeras, and analysed the MHC restriction specificity in proliferation and cytotoxicity assays. The cytotoxicity of all the clones was primarily host-MHC restricted. However, the CTL clones proliferated to viral antigen presented by both donor- or host-MHC. Our model allowed CTL cloning by cross-specific stimulation with antigen plus either donor-MHC or else host-MHC. Interestingly, even the 14 CTL clones which had been raised with donor-MHC systematically killed host-MHC but not donor-MHC expressing cells. Thus, after BMT, CTLs may proliferate crossreactively to donor-MHC but cytolysis is predominantly directed to host-MHC expressing cells. Since lytic CTL activity probably reflects high avidity CTL interaction necessary for viral clearance in vivo, the data suggest that the donor-MHC restricted CTL activity may not be protective and that virus may escape CTL surveillance in donor cells.
Sujets
PID Serval
serval:BIB_26391837BDDA
PMID
Date de création
2008-01-28T10:32:58.755Z
Date de création dans IRIS
2025-05-20T15:17:15Z