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 CD8α− DCs, whereas 15 hours later they are presented mainly by CD8α+ DCs. After PPV-VLPs processing, a fraction of CD11b+ DCs undergo phenotypic changes, i.e., the up-regulation of CD8α and CD205 and the loss of CD4 molecules on their surface. The failure to detect mRNA coding for CD8α in CD11b+ DCs suggests that CD8α expression by these cells is not due to de novo synthesis. In recombination-activating gene knockout mice (Rag−/−), CD11b+ DCs did not express CD8α and PPV-VLPs presentation by CD8α+ DCs was severely diminished. These results indicate that both CD8α− and CD8α+ DCs play an important role in the induction of CTL responses by exogenous antigens, such as VLP.
CD8α2 CD11b+ Dendritic Cells Present Exogenous Virus-like Particles to CD8+ T Cells and Subsequently Express CD8α and CD205 Molecules
I. Casal's present address is Programa de Biotecnología, Centro Nacional de Investigaciones Oncológicas, 28029 Madrid, Spain.
Abbreviations used in this paper: β2M, β2-microglobulin; DC, dendritic cell; LCMV, lymphocytic choriomeningitis virus; MACS, magnetic-activated cell sorting; OVA257–264, peptide corresponding to the sequence of amino acids 257–264 of the chicken egg albumin; PPV, porcine parvovirus; PPV-VLPss-OVA, PPV virus-like particles carrying OVA257–264; Rag, recombination-activating gene; RT, reverse transcription; TAP, transporter associated with antigen processing; VLP, virus-like particle; VP, viral protein.
Gabriel Morón, Paloma Rueda, Ignacio Casal, Claude Leclerc; CD8α2 CD11b+ Dendritic Cells Present Exogenous Virus-like Particles to CD8+ T Cells and Subsequently Express CD8α and CD205 Molecules . J Exp Med 20 May 2002; 195 (10): 1233–1245. doi: https://doi.org/10.1084/jem.20011930
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