Host CD4+ T lymphocytes are required for the synergistic action of interferon-alpha/beta and adoptively transferred immune cells in the inhibition of visceral ESb metastases.
Effective adoptive immunotherapy of immunocompetent DBA/2 mice challenged i.v. with the highly metastatic ESb T-cell lymphoma required the combined treatment of recipient mice with tumor-sensitized spleen cells and IFN-alpha/beta. In contrast, immune spleen cells and IFN-alpha/beta treatment did not increase the survival time of ESb-injected DBA/2-nu/nu mice, DBA/2-bg/bg mice, or normal DBA/2 mice injected with antibody to CD4. Treatment of immunocompetent DBA/2 mice with antibody to asialo-GM1, silica, dichloromethylene diphosphonate-containing liposomes, or 500 rads whole-body gamma-irradiation did not diminish the antimetastatic action of ESb-immune cells and IFN-alpha/beta. These results indicate that adoptively transferred immune T lymphocytes and IFN-alpha/beta act together with host CD4+ T lymphocytes/factors to inhibit ESb visceral metastases. Combined treatment with ESb-immune cells together with interleukin-1 beta (IL-1 beta), IL-2, tumor necrosis factor-alpha, or granulocyte-macrophage colony-stimulating factor did not increase the survival time of normal DBA/2 mice challenged with ESb cells. In contrast, IL-12, which had only a slight antimetastatic effect when 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 mice with potent antibody to IFN-alpha/beta did not abrogate the capacity of IL-12 and ESb-immune spleen cells to inhibit ESb metastases. Unlike immunotherapy with ESb-immune cells and IFN-alpha/beta, ESb-immune cells together with IL-12 inhibited ESb metastases in immunodeficient DBA/2-bg/bg mice.
Unite Propre de Recherche, Centre National de la Recerche Scientifique 9045 Institut Federatif de Cancer 1, Villejuif, France.
T J
TJ
Kaido
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C
Maury
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I
Gresser
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D007111:Immunity, Cellular; D007116:Immunization, Passive; D007167:Immunotherapy; D007370:Interferon Type I / Q000008:administration & dosage*; D007371:Interferon-gamma / Q000502:physiology; D018664:Interleukin-12 / Q000502:physiology; D008223:Lymphoma / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008811:Mice, Inbred DBA; D008817:Mice, Mutant Strains; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D014407:Tumor Cells, Cultured
D007370:Interferon Type I; D018664:Interleukin-12; D007371:Interferon-gamma