The response of human dendritic cells to recombinant adenovirus, recombinant Mycobacterium bovis Bacillus Calmette Guerin and biolistic methods of antigen delivery: different induction of contact-dependant and soluble signals

Dendritic cells (DCs) are the most potent antigen presenting cells for indu cing T-cell immune responses. The ability to grow human DCs from monocyte p recursors provides an abundant source of these cells, which can be modified in vitro to present antigens. Re-administration of modified DCs to patient s as vaccines has been shown in some cases to induce immune responses again st cancer and infectious disease. Gene delivery to DCs provides an intracel lular source of antigen for efficient and persistent loading of major histo compatibility complex (MHC) class I molecules. The aim of this study was to use monocyte-derived DCs (MD-DCs) from healthy donors to compare in vitro gene transfer, mediated by adenovirus, M. bovis Bacillus Calmette Guerin (B CC) and biolistic delivery. Efficiency of transfection and effect on DC phe notype, allostimulatory capacity and cytokine secretion was investigated. A denovirus and BCG both showed a comparable ability to transfect MD-DCs, whe reas the biolistic delivery by gene gun was unsuccessful in the reporter ge ne delivery. BCG transfection promoted MD-DC maturation as is apparent in t he surface phenotype, allostimulatory capacity and cytokine secretion from cells. In comparison, adenovirus and biolistic delivery had a I-educed effe ct on MD-DCs although enhancement of co-stimulatory and MHC molecule expres sion occurred in the cells of some donors. Both BCG and adenovirus represen t useful vectors for gene transfer to human DCs. The effect of BCG on DC ma turation may provide additional signals for the induction of antigen-specif ic T-cell responses. (C) 2001 Elsevier Science B.V. All rights reserved.