DENDRITIC CELLS, INTERLEUKIN-12, AND CD4(-RESTRICTED REACTIVITY TO A TUMOR() LYMPHOCYTES IN THE INITIATION OF CLASS I)SELF PEPTIDE/

Cell-mediated immunity involving CD8(+) lymphocytes is effective in me diating rejection of murine mastocytoma cells bearing P815AB, a tumor- associated and self antigen showing similarity to tumor-specific share d antigens in humans. Although this antigen may act as an efficient ta rget for class I-restricted responses in immunized mice, neither P815A B expressed on tumor cells nor a related synthetic nonapeptide will ac tivate unprimed CD8(+) cells for in who reactivity, measured by skin t est assay. We review evidence showing that the failure of P815AB to in itiate CD8(+) cell reactivity may be due to defective recruitment of a ccessory and Th1-like cells to the afferent phase of the response init iated by transfer of mice with dendritic cells pulsed in vitro with th e P815AB peptide. Although the co-presence of a T helper peptide in de ndritic cell priming in vitro with P815AB may compensate for the poor generation of accessory and Th1 cells in the adoptively transferred mi ce, recombinant IL-12 can replace the helper peptide in both effects. Effective priming to P815AB in vivo is achieved by either exposing den dritic cells to IL-12 prior to P815AB priming or administering the rec ombinant cytokine in vivo. Different approaches suggest that IL-12 may act both on accessory cells to improve presentation of previously und escribed class II-restricted epitopes of P815AB and on CD4(+) cells to improve recognition of such epitopes. In particular, at the CD4(+) ce ll level, IL-12 apparently acts as an adjuvant and an inhibitor of ane rgy induction. These data offer useful information for developing vacc ination strategies using dendritic cells and class I-restricted tumor peptides in humans.