HOST CD4(-LYMPHOCYTES ARE REQUIRED FOR THE SYNERGISTIC ACTION OF INTERFERON-ALPHA() T)BETA AND ADOPTIVELY TRANSFERRED IMMUNE CELLS IN THE INHIBITION OF VISCERAL ESB METASTASES/

Effective adoptive immunotherapy of immunocompetent DBA/2 mice challen ged i.v. with the highly metastatic ESb T-cell lymphoma required the c ombined treatment of recipient mice with tumor-sensitized spleen cells and IFN-alpha/beta, In contrast, immune spleen cells and IFN-alpha/be ta treatment did not increase the survival time of ESb-injected DBA/2- nu/nu mice, DBA/2bg/bg mice, or normal DBA/2 mice injected with antibo dy to CD4, Treatment of immunocompetent DBA/2 mice with antibody to as ialo-GM1, silica, dichloromethylene diphosphonate-containing liposomes , or 500 rads whole-body gamma-irradiation did not diminish the antime tastatic action of ESb-immune cells and IFN-alpha/beta. These results indicate that adoptively transferred immune T lymphocytes and IFN-alph a/beta act together with host CD4(+) T lymphocytes/factors to inhibit ESb visceral metastases. Combined treatment with ESb-immune cells toge ther with interleukin-1 beta (IL-1 beta), IL-2, tumor necrosis factor- alpha, or granulocyte-macrophage colony-stimulating factor did not inc rease the survival time of normal DBA/2 mice challenged with ESb cells , In contrast, IL-12, which had only a slight antimetastatic effect wh en administered alone, did synergize with ESb-immune spleen cells and increased the survival time of ESb-challenged mice to a similar extent as did IFN-alpha/beta and immune spleen cells, Treatment of DBA/2 mic e with potent antibody to IFN-alpha/beta did not abrogate the capacity of IL-12 and ESb-immune spleen cells to inhibit ESb metastases. Unlik e immunotherapy with ESb-immune cells and IFN-alpha/beta, ESb-immune c ells together with IL-12 inhibited ESb metastases in immunodeficient D BA/2-bg/bg mice.