Identification of a Clinical-Grade Maturation Factor for Dendritic Cells
作者:
Claire Boccaccio,
Sylvie Jacod,
Andrew Kaiser,
Aurélie Boyer,
Jean-Pierre Abastado,
Alessandra Nardin,
期刊:
Journal of Immunotherapy
(OVID Available online 2002)
卷期:
Volume 25,
issue 1
页码: 88-96
ISSN:1524-9557
年代: 2002
出版商: OVID
关键词: Dendritic cells;Maturation;Adjuvants;Cytokines;Immunotherapy
数据来源: OVID
摘要:
Dendritic cells (DC) are essential for the generation of primary adaptive immune responses, but their full immunostimulatory capacities are only reached upon maturation. The authors compared several clinical-grade adjuvants of bacterial origin to determine their ability to induce phenotypic and functional maturation of monocyte-derived DC (Dendritophages, D&phis;; IDM, Paris, France) differentiated with granulocyte-macrophage colony-stimulating factor and interleukin-13 in single-use cell processors (VacCell; IDM, Paris, France). Monophosphoryl lipid A,Mycobacterium bovisbacillus Calmette-Guérin, and Ribomunyl (Pierre Fabre Medicament, Boulogne, France) all appeared able to provide the signal necessary to initiate D&phis; maturation. However, only Ribomunyl (Pierre Fabre Medicament) (containing membrane and ribosomal fractions from four bacterial strains) allowed the authors to obtain a significant enhancement of allostimulatory abilities and cytokine production by D&phis; in the absence of active cellular infection. Addition of interferon-gamma (IFN-&ggr;) to Ribomunyl resulted in more pronounced upregulation of CD83, major histocompatibility complex class I, and B7 molecules by D&phis;. Moreover, the IFN-&ggr; addition modulated their cytokine secretion, allowing higher levels of bioactive interleukin-12 concomitant with lower levels of interleukin-10. In kinetic studies, D&phis; contact with Ribomunyl and IFN-&ggr; for 6 hours was sufficient to trigger a maturation process that completed spontaneously. Thus, Ribomunyl in association with IFN-&ggr; represents a suitable agent for the ex vivo production of mature monocyte-derived DC that can be used as cellular vaccines to promote a potent type 1 immune response.
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