Tumor-specific T cells which form clusters with dendritic cells and tumor cells and deliver macrophage-activating...

T cells prepared from tumor (Meth A)-bearing mice were cocultured with homologous tumor cells and splenic dendritic cells to enrich tumor-specific T cells by the separation of clusters. T blasts generated from clusters were capable of inhibiting the in vivo tumor cell growth. The culture supernatant of clustering cells (CLSN) was effective in activating macrophages (M phi) to be cytostatic and cytocidal against tumor cells. Moreover, it was found that CLSN contains at least 3 distinct factors; one was identified as interferon-gamma (IFN-gamma), and the others are so far unidentified, but one acts synergistically with IFN-gamma, possibly as the second signal, and the other cooperates with lipopolysaccharide but not with IFN-gamma. We propose that the tumor-specific T cells secrete soluble mediators which cooperate with each other in M phi activation against tumor cells.