IL-12 controls cytotoxicity of a novel subset of self-antigen-specific human CD28+ cytolytic T cells.

Détails

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Etat: Public
Version: Final published version
ID Serval
serval:BIB_34A31269CA86
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
IL-12 controls cytotoxicity of a novel subset of self-antigen-specific human CD28+ cytolytic T cells.
Périodique
Journal of Immunology
Auteur⸱e⸱s
Barbey C., Baumgaertner P., Devevre E., Rubio-Godoy V., Derre L., Bricard G., Guillaume P., Luescher I.F., Liénard D., Cerottini J.C., Romero P., Rufer N., Speiser D.E.
ISSN
0022-1767 (Print)
ISSN-L
0022-1767
Statut éditorial
Publié
Date de publication
2007
Peer-reviewed
Oui
Volume
178
Numéro
6
Pages
3566-3574
Langue
anglais
Résumé
Activated CD8 T cells develop cytotoxicity against autologous cells bearing foreign Ags and self/tumor Ags. However, self-specific cytolysis needs to be kept under control to avoid overwhelming immunopathology. After peptide vaccination of melanoma patients, we studied molecular and functional properties of T cell subsets specific for the self/tumor Ag Melan-A/MART-1. Ex vivo analysis revealed three Ag-specific effector memory (EM) populations, as follows: CD28-negative EM (EM28(-)) T cells strongly expressing granzyme/perforin, and two EM28(+) subsets, one with high and the other with low level expression of these cytotoxic proteins. For further functional characterization, we generated 117 stable CD8 T cell clones by ex vivo flow cytometry-based sorting of these subsets. All EM28(-)-derived clones lysed target cells with high efficacy. In contrast, EM28(+)-derived clones were heterogenous, and could be classified in two groups, one with high and the other with low killing capacity, correlating with granzyme/perforin expression. High and low killer phenotypes remained surprisingly stable for several months. However, strongly increased granzyme expression and cytotoxicity were observed after exposure to IL-12. Thus, the data reveal a newly identified subset of CD28(+) conditional killer T cells. Because CD28 can mediate strong costimulatory signals, tight cytotoxicity control, as shown in this study through IL-12, may be particularly important for subsets of T cells expressing CD28.
Mots-clé
Adjuvants, Immunologic/pharmacology, Antigens, CD28/biosynthesis, Antigens, CD28/immunology, Antigens, Neoplasm/administration & dosage, Antigens, Neoplasm/immunology, CD8-Positive T-Lymphocytes/immunology, CD8-Positive T-Lymphocytes/metabolism, Clone Cells, Female, Granzymes/biosynthesis, Granzymes/immunology, Humans, Immunity, Cellular/drug effects, Interleukin-12/pharmacology, Isoantigens/administration & dosage, Isoantigens/immunology, Male, Melanoma/immunology, Melanoma/metabolism, Membrane Glycoproteins/biosynthesis, Membrane Glycoproteins/immunology, Peptide Fragments/administration & dosage, Peptide Fragments/immunology, Perforin, Pore Forming Cytotoxic Proteins/biosynthesis, Pore Forming Cytotoxic Proteins/immunology, Time Factors, Vaccination
Pubmed
Web of science
Open Access
Oui
Création de la notice
18/04/2008 11:03
Dernière modification de la notice
20/08/2019 13:21
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