Dendritic cells infected with recombinant defective adenoviruses undergo NF-kB activation and partial maturation

  1. M. Duarte 1
  2. P. Boya 1
  3. M. Rodríguez Calvillo 1
  4. I. Narvaiza 1
  5. J.J. Lasarte 1
  6. E. Larrea 1
  7. M. P. Civeira 1
  8. J. Prieto 1
  9. I. Melero 1
  1. 1 Division of Gene Therapy and Hepatology. Department of Medicine. University of Navarra. Pamplona. Spain
Journal:
INMUNOLOGÍA

ISSN: 0213-9626

Year of publication: 2001

Volume: 20

Issue: 3

Pages: 130-142

Type: Article

GOOGLE SCHOLAR

More publications in: INMUNOLOGÍA

Abstract

Dendritic cells (DC) are being used as natural adjuvantsto induce therapeutically useful immune responses. To achieveso, DC are often provided with relevant antigens by genetransfection using diff e rent viral and non-viral vectors.Recombinant defective adenoviruses encoding antigens orcytokines have been used to transfer genes to DC to enhanceimmune responses. We have studied the effects of infectingc u l t u red human or murine DC with first generation re c o mbinant adenovirus containing the re p o rter gene b- g a l a c t o s idase (AdCMVLacZ). AdCMVLacZ infection induced nucleartranslocation of diff e rent NF-kB members by triggeringp h o s p h o rylation of IkB-a as shown by electro p h o retic mobility shift assay and western blot results. NF-kB activationwas also induced by semipurified viral capsides or similara d e n o v i rus without transgene, but not by a similar adenovirus encoding for a dominant inhibitor of NF-kB( A d C M V IkB). AdCMVLacZ infection, in contrast toA d C M V IkB, induces in DC strong upregulation of CD40accompanied by increases of CD80 and CD86, but with lesssignificant increases in surface expression of MHC class II.A d e n o v i rus-induced phenotypic changes re n d e red DC moreactive to induce proliferation of allogeneic T- l y m p h o c y t e sand made DC secrete IL-6 without detectable levels of othercytokines such as TNFa and IL-12. Our results show thatrecombinant adenovirus trigger, in a transgene independentfashion, changes in the maturation status of both human andmurine DC, which are relevant to their function.