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Prepublished online as a Blood First Edition Paper on June 5, 2003; DOI 10.1182/blood-2003-03-0748.
Submitted March 10, 2003
Accepted June 2, 2003
A dendritic cell vaccine against invasive aspergillosis in allogeneic hematopoietic transplantation
Silvia Bozza, Katia Perruccio, Claudia Montagnoli, Roberta Gaziano, Silvia Bellocchio, Emanuela Burchielli, Gabriel Nkwanyuo, Lucia Pitzurra, Andrea Velardi, and Luigina Romani*
Dept. of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy
Dept. of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy
* Corresponding author; email: lromani{at}unipg.it.
Dendritic cells (DCs) have a remarkable functional plasticity in response to conidia and hyphae of the fungus Aspergillus fumigatus. In the present study we sought to assess the capacity of DCs activated by live fungi or fungal RNA to generate antifungal immunity in vivo. It was found that both human and murine DCs pulsed with live fungi or transfected with fungal RNA underwent functional maturation, as revealed by the up-regulated expression of histocompatibility class II antigen and costimulatory molecules and the production of IL-12 in response to conidia or conidial RNA and of IL-4/IL-10 in response to hyphae or hyphal RNA. DCs pulsed with conidia or transfected with conidial RNA activated antigen-specific, interferon (IFN)- -producing T lymphocytes in vitro and in vivo upon adoptive transfer in mice otherwise susceptible to aspergillosis. TH1-dependent antifungal resistance could also be induced in allogeneic bone marrow-transplanted mice and was associated with an accelerated recovery of myeloid and lymphoid cells. As the efficacy of the infusion of DCs was superior to that obtained upon the adoptive transfer of Aspergillus-specific T cells, these results point out the vaccinating potential of DCs pulsed with Aspergillus conidia or conidial RNA in hematopoietic transplantation.
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