Definition of key variables for the induction of optimal NY-ESO-1-specific T cells in HLA transgene mice.

Détails

ID Serval
serval:BIB_FF2FB8BC9031
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Definition of key variables for the induction of optimal NY-ESO-1-specific T cells in HLA transgene mice.
Périodique
Journal of Immunology
Auteur⸱e⸱s
Johannsen A., Genolet R., Legler D.F., Luther S.A., Luescher I.F.
ISSN
1550-6606[electronic], 0022-1767[linking]
Statut éditorial
Publié
Date de publication
2010
Peer-reviewed
Oui
Volume
185
Numéro
6
Pages
3445-3455
Langue
anglais
Résumé
An attractive treatment of cancer consists in inducing tumor-eradicating CD8(+) CTL specific for tumor-associated Ags, such as NY-ESO-1 (ESO), a strongly immunogenic cancer germ line gene-encoded tumor-associated Ag, widely expressed on diverse tumors. To establish optimal priming of ESO-specific CTL and to define critical vaccine variables and mechanisms, we used HLA-A2/DR1 H-2(-/-) transgenic mice and sequential immunization with immunodominant DR1- and A2-restricted ESO peptides. Immunization of mice first with the DR1-restricted ESO(123-137) peptide and subsequently with mature dendritic cells (DCs) presenting this and the A2-restriced ESO(157-165) epitope generated abundant, circulating, high-avidity primary and memory CD8(+) T cells that efficiently killed A2/ESO(157-165)(+) tumor cells. This prime boost regimen was superior to other vaccine regimes and required strong Th1 cell responses, copresentation of MHC class I and MHC class II peptides by the same DC, and resulted in upregulation of sphingosine 1-phosphate receptor 1, and thus egress of freshly primed CD8(+) T cells from the draining lymph nodes into circulation. This well-defined system allowed detailed mechanistic analysis, which revealed that 1) the Th1 cytokines IFN-gamma and IL-2 played key roles in CTL priming, namely by upregulating on naive CD8(+) T cells the chemokine receptor CCR5; 2) the inflammatory chemokines CCL4 (MIP-1beta) and CCL3 (MIP-1alpha) chemoattracted primed CD4(+) T cells to mature DCs and activated, naive CD8(+) T cells to DC-CD4 conjugates, respectively; and 3) blockade of these chemokines or their common receptor CCR5 ablated priming of CD8(+) T cells and upregulation of sphingosine 1-phosphate receptor 1. These findings provide new opportunities for improving T cell cancer vaccines.
Pubmed
Web of science
Création de la notice
14/09/2010 15:44
Dernière modification de la notice
20/08/2019 17:29
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