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Identification of a Clinical-Grade Maturation Factor for Dendritic Cells

2002; Lippincott Williams & Wilkins; Volume: 25; Issue: 1 Linguagem: Inglês

10.1097/00002371-200201000-00010

1537-4513

Claire Boccaccio, Sylvie Jacod, Andrew Kaiser, Aurélie Boyer, Jean‐Pierre Abastado, Alessandra Nardin,

Antimicrobial Peptides and Activities

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, Dφ; 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 bovis bacillus Calmette-Guérin, and Ribomunyl (Pierre Fabre Medicament, Boulogne, France) all appeared able to provide the signal necessary to initiate Dφ 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 Dφ in the absence of active cellular infection. Addition of interferon-gamma (IFN-γ) to Ribomunyl resulted in more pronounced upregulation of CD83, major histocompatibility complex class I, and B7 molecules by Dφ. Moreover, the IFN-γ addition modulated their cytokine secretion, allowing higher levels of bioactive interleukin-12 concomitant with lower levels of interleukin-10. In kinetic studies, Dφ contact with Ribomunyl and IFN-γ for 6 hours was sufficient to trigger a maturation process that completed spontaneously. Thus, Ribomunyl in association with IFN-γ 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.