Dual function of Drosophila cells as APCs for naive CD8(+) T cells: Implications for tumor immunotherapy

With unseparated mouse spleen cells as responders, Drosophila cells expressing MHC class I (L(d)) molecules alone lead to peptide-specific responses of CD8(+) cells in the absence of exogenous cytokines. Under these conditions, DNA released from dying cells stimulates the B cells in spleen to up-regulate costimulatory molecules; these activated B cells then provide bystander costimulation for CD8(+) cells responding to class I-peptide complexes on the Drosophila APCs. By stimulating B cells and presenting antigen to T cells, Drosophila cells thus serve two different functions in promoting primary responses of CD8(+) cells in vitro. With this system, we show that L(d)-transfected Drosophila cells are able to induce autologous spleen cells to respond to a tumor-specific peptide in vitro and, after transfer, cause tumor rejection in vivo.