CD8alpha- CD11b+ dendritic cells present exogenous virus-like particles (VLPs) to CD8+ T cells and subsequently express CD8a and DEC205 molecules

GABRIEL MORÓN; PALOMA RUEDA; IGNACIO CASAL; CLAUDE LECLERC

JOURNAL OF EXPERIMENTAL MEDICINE

ROCKEFELLER UNIV PRESS

Año: 2002 vol. 195 p. 1233 - 1245

0022-1007

Recombinant porcine parvovirus virus-like particles (PPV-VLPs) are particulate exogenous antigens that induce a strong, specific cytotoxic T lymphocyte (CTL) response in the absence of adjuvant. In the present report, we demonstrate in vivo that dendritic cells (DCs) present PPV-VLPs to CD8 T cells after intracellular processing. PPV-VLPs are captured by DCs with a high efficacy, which results in the delivery of these exogenous antigens to 50% of the whole spleen DC population. In vivo, a few hours after injection, PPV-VLPs are presented exclusively to CD8 T cells by CD8 DCs, whereas 15 hours later they are presented mainly by CD8 DCs. After PPV-VLPs processing, a fraction of CD11b DCs undergo phenotypic changes, i.e., theup-regulation of CD8 and CD205 and the loss of CD4 molecules on their surface. The failureto detect mRNA coding for CD8 in CD11b DCs suggests that CD8 expression bythese cells is not due to de novo synthesis. In recombination-activating gene knockout mice(Rag -/-), CD11b DCs did not express CD8 and PPV-VLPs presentation by CD8 DCswas severely diminished. These results indicate that both CD8 and CD8 DCs play an importantrole in the induction of CTL responses by exogenous antigens, such as VLP.