Transgenic expression of Ly49A on T cells impairs a specific antitumor response.

Détails

ID Serval
serval:BIB_8D644545DCE9
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Transgenic expression of Ly49A on T cells impairs a specific antitumor response.
Périodique
Journal of immunology
Auteur(s)
Brawand P., Lemonnier F.A., MacDonald H.R., Cerottini J.C., Held W.
ISSN
0022-1767
Statut éditorial
Publié
Date de publication
2000
Peer-reviewed
Oui
Volume
165
Numéro
4
Pages
1871-1876
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Inhibitory MHC receptors determine the reactivity and specificity of NK cells. These receptors can also regulate T cells by modulating TCR-induced effector functions such as cytotoxicity, cytokine production, and proliferation. Here we have assessed the capacity of mouse T cells expressing the inhibitory MHC class I receptor Ly49A to respond to a well-defined tumor Ag in vivo using Ly49A transgenic mice. We find that the presence of Ly49A on the vast majority of lymphocytes prevents the development of a significant Ag-specific CD8+ T cell response and, consequently, the rejection of the tumor. Despite minor alterations in the TCR repertoire of CD8+ T cells in the transgenic lines, precursors of functional tumor-specific CD8+ T cells exist but could not be activated most likely due to a lack of appropriate CD4+ T cell help. Surprisingly, all of these effects are observed in the absence of a known ligand for the Ly49A receptor as defined by its ability to regulate NK cell function. Indeed, we found that the above effects on T cells may be based on a weak interaction of Ly49A with Kb or Db class I molecules. Thus, our data demonstrate that enforced expression of a Ly49A receptor on conventional T cells prevents a specific immune response in vivo and suggest that the functions of T and NK cells are differentially sensitive to the presence of inhibitory MHC class I receptors.
Mots-clé
Animals, Antigens, Ly, Antigens, Viral/immunology, CD4-Positive T-Lymphocytes/immunology, CD8-Positive T-Lymphocytes/immunology, Carrier Proteins/biosynthesis, Carrier Proteins/genetics, Dose-Response Relationship, Immunologic, Epitopes, T-Lymphocyte/immunology, Gene Expression Regulation/immunology, Graft Rejection/genetics, Graft Rejection/immunology, H-2 Antigens/metabolism, Immunodominant Epitopes/immunology, Lectins, C-Type, Leukemia, Experimental/immunology, Leukemia, Experimental/prevention &amp, control, Lymphocyte Activation/genetics, Lymphopenia/genetics, Lymphopenia/immunology, Membrane Proteins/biosynthesis, Membrane Proteins/genetics, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Moloney murine leukemia virus/immunology, NK Cell Lectin-Like Receptor Subfamily A, Neoplasm Transplantation, Receptors, Immunologic/biosynthesis, Receptors, Immunologic/genetics, Receptors, NK Cell Lectin-Like, T-Lymphocytes/immunology, T-Lymphocytes/metabolism, Transgenes/immunology, Tumor Cells, Cultured/immunology, Tumor Cells, Cultured/transplantation
Pubmed
Web of science
Création de la notice
28/01/2008 12:13
Dernière modification de la notice
03/03/2018 19:15
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