MURINE DENDRITIC CELLS LOADED IN-VITRO WITH SOLUBLE-PROTEIN PRIME CYTOTOXIC T-LYMPHOCYTES AGAINST TUMOR-ANTIGEN IN-VIVO

The printing of an immune response against a major histocompatibility complex class I-restricted antigen expressed by nonhematopoietic cells involves the transfer of that antigen to a host bone marrow-derived a ntigen presenting cell (APC) for presentation to CD8(+) T lymphocytes. Dendritic cells (DC), as bone marrow-derived APC, are first candidate s for presentation oftumorassociated antigens (TAA). The aim of this s tudy was to see whether DC 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 of beta-g alactosidase (beta-gal)-transduced tumor cell, lines as a model in whi ch beta-gal operationally functions as TAA. For in vivo priming both a DC line, transduced or not transduced with the gene coding for murine GM-CSF, and fresh bone marrow-derived DC (bm-DC), loaded in vitro wit h soluble beta-gal, were used. Priming with either granulocyte macroph age colony-stimulating factor-transduced DC line or fresh bm-DC but no t with untransduced DC line generated CTL able to lyse beta-gal-transf ected target cells. Furthermore, GM-CSF was necessary for the DC line to efficiently present soluble beta-gal as an H-2L(d)-restricted pepti de to a beta-gal-specific CTL clone. Data also show that a long-lastin g immunity against tumor challenge can be induced using beta-gal-pulse d bm-DC as vaccine. These results indicate that effector cells can be recruited and activated in vivo by antigen-pulsed DC, providing an eff icient immune reaction against tumors.