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DNA vaccination with all-trans retinoic acid treatment induces long-term survival and elicits specific immune responses requiring CD4+ and CD8+ T-cell activation in an acute promyelocytic leukemia mouse model
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SYSNO ASEP 0335722 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title DNA vaccination with all-trans retinoic acid treatment induces long-term survival and elicits specific immune responses requiring CD4+ and CD8+ T-cell activation in an acute promyelocytic leukemia mouse model Author(s) Furugaki, K. (FR)
Pokorná, Kateřina (UMG-J)
le Pogam, C. (FR)
Aoki, M. (FR)
Reboul, M. (FR)
Bajzik, V. (FR)
Krief, P. (FR)
Janin, A. (FR)
Noguera, M.-E. (FR)
West, R. (GB)
Charron, D. (FR)
Chomienne, C. (FR)
Pla, M. (FR)
Moins-Teisserenc, H. (FR)
Padua, R.A. (FR)Number of authors 15 Source Title Blood. - : American Society of Hematology - ISSN 0006-4971
Roč. 115, č. 3 (2010), s. 653-656Number of pages 4 s. Language eng - English Country US - United States Keywords all-trans retinoic acid ; DNA vaccination ; protective immunity Subject RIV EB - Genetics ; Molecular Biology CEZ AV0Z50520514 - UMG-J (2005-2011) UT WOS 000273820600027 DOI 10.1182/blood-2007-08-109009 Annotation DNA vaccination and all-trans retinoic acid (ATRA) bring survival advantage in a mouse model of acute promyelocytic leukemia (APL). Depletion of CD4+ or CD8+ cells abolished this effect. CD4+ depletions of long-term survivors resulted in relapse and death within 3 months, thus demonstrating need of both cell subsets for generation of DNA-driven antileukemic immune responses and underscoring a crucial role of CD4+ cells in maintenance of durable remissions. Degranulation and cytotoxic carboxyfluorescein diacetate succinimidyl ester-based assays showed MHC-restricted APL-specific T cell-mediated immune responses. Sorted APL-specific CD8+CD107a+ T cells showed increased antileukemic activity. Effectors from ATRA + DNA-treated mice were shown to secrete IFN-g when stimulated with APL cells or peptides from the PL-RARa vaccine-derived sequences as shown by ELISpot assays. DNA vaccination with ATRA thus confers effective boosting of IFN-g-producing and cytotoxic T cells in leukemic mice. Workplace Institute of Molecular Genetics Contact Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Year of Publishing 2010
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