Ant igen In Vivo

The priming of an immune response against a major histocompatibility complex class I-restricted antigen expressed by nonhematopoietic cells involves the transfer o f that antigen to a host bone marrow-derived antigen presenting cell (APC) for presentation to CD8 + T lymphocytes. Dendritic cells (DC), as bone marrow-derived APC, are first candidates for presentation o f tumorassociated antigens (TAA). The aim of this study was to see whether D C are able to prime in vivo antigen-specific cytotoxic T lymphocytes after exposure to a soluble protein antigen in vitro. Lacking a well-defined murine TAA, we took advantage o f 13-galactosidase (13-gal)transduced tumor cell lines as a model in which [3-gal operationally functions as TAA. For in vivo priming both a D C line, transduced or not transduced with the gene coding for murine GM-CSF, and fresh bone marrow-derived D C (bm-DC), loaded in vitro with soluble ~-gal, were used. Priming with either granulocyte macrophage colony-stimulating factor-transduced D C line or fresh b m D C but not with untransduced D C line generated CTL able to lyse 13-gal-transfected target cells. Furthermore, GM-CSF was necessary for the D C line to efficiently present soluble [3-gal as an H-2Ld-restricted peptide to a [3-gal--specific CTL clone. Data also show that a long-lasting immunity against tumor challenge can be induced using [3-gal-pulsed b m D C as vaccine. These results indicate that effector cells can be recruited and activated in vivo by antigen-pulsed DC, providing an efficient immune reaction against