Dendritic cells (DCs) are capable of capturing exogenous Ag for the generation of MHC class I/peptide complexes. For efficient activation of memory CD8+ T cells to occur via a cross-presentation pathway, DCs must receive helper signals from CD4+ T cells. Using an in vitro system that reflects physiologic recall memory responses, we have evaluated signals that influence helper-dependent cross-priming, while focusing on the source and cellular target of such effector molecules. Concerning the interaction between CD4+ T cells and DCs, we tested the hypothesis that CD40 engagement on DCs is critical for IL-12p70 (IL-12) production and subsequent stimulation of IFN-γ release by CD8+ T cells. Although CD40 engagement on DCs, or addition of exogenous IL-12 are both sufficient to overcome the lack of help, neither is essential. We next evaluated cytokines and chemokines produced during CD4+ T cell/DC cross talk and observed high levels of IL-2 produced within the first 18–24 h of Ag-specific T cell engagement. Functional studies using blocking Abs to CD25 completely abrogated IFN-γ production by the CD8+ T cells. Although required, addition of exogenous IL-2 did not itself confer signals sufficient to overcome the lack of CD4+ T cell help. Thus, these data support a combined role for Ag-specific, cognate interactions at the CD4+ T cell/DC as well as the DC/CD8+ T cell interface, with the helper effect mediated by soluble noncognate signals.

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Resident, inflammatory or bone-marrow macrophages from C57Bl/6 mice incubated in vitro with a pure human urinary protein (HGP.43) decreased the growth rate of Lewis tumor cells (3LL). This inhibition of 3LL growth was the result of a cytotoxic activity of these macrophages which was independent of oxygen metabolites and nitrous oxide. Murine monoclonal antibodies (MAbs) against HGP.43 inhibited macrophage-mediated cytotoxicity. This cytotoxic activity was not due to the release of cytotoxic factors in the culture supernatant, showing that a contact between macrophages and tumor cells was required to express cytotoxicity. The presence of HGP.43 was absolutely necessary during the incubation of macrophages with target cells. In vivo, in HGP.43-treated mice, the growth of the primary tumor was not delayed but the size and number of lung metastases were significantly reduced 21 days after tumor inoculation.