Host humoral and cellular immune mechanisms in the continued suppression of Friend erythroleukemia metastases after interferon alpha/beta treatment in mice.
DBA/2 mice were injected intravenously with 2 x 10(6) 3C18 Friend erythroleukemia cells (FLC), a cell line resistant to interferon alpha/beta (IFN-alpha/beta). Although daily administration of mouse IFN-alpha/beta markedly increased the mean survival time, most IFN-treated mice continued to harbor FLC in different organs. To investigate the mechanisms responsible for this persistent suppression of FLC growth in IFN-treated mice, we undertook a series of adoptive transfer experiments with sera and spleen cells. Sera from FLC-injected, IFN-treated mice were very effective in conferring protection on DBA/2 mice even when injected systemically (intravenously) 18-24 h before intravenous challenge with FLC. These sera also exhibited antitumor activity when injected subcutaneously or intraperitoneally together with FLC. The protective factor in serum was shown to be an immunoglobulin. FLC-injected, IFN-treated mice developed antibodies to FLC demonstrable by radioimmunoassay and complement-dependent cytotoxicity. Sera from these mice recognized a specific 65-kD FLC membrane antigen(s) not detectable on membrane extracts from RBL-5 or ESb tumor cells, or on normal spleen cells. FLC-injected, IFN-treated mice also developed a specific cellular response demonstrable by transfer of protection with spleen cells injected intravenously or subcutaneously. Analysis of the responsible spleen cell populations indicated that the effector cells were neither T nor B cells. These results demonstrating the importance of host humoral and cellular immune mechanisms in the persistent suppression of FLC in IFN-treated mice may be relevant to the use of IFN-alpha/beta in patients in whom tumors may regress and tumor cells may then remain latent for extended periods of time.
Gresser
I
I
Institut de Recherches Scientifiques sur le Cancer, Centre National de la Recherche Scientifique, Villejuif, France.
Carnaud
C
C
Maury
C
C
Sala
A
A
Eid
P
P
Woodrow
D
D
Maunoury
M T
MT
Belardelli
F
F
D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis / Q000276:immunology; D002460:Cell Line; D005622:Friend murine leukemia virus / Q000276:immunology / Q000302:isolation & purification / Q000502:physiology*; D007111:Immunity, Cellular / Q000187:drug effects / Q000502:physiology*; D007165:Immunosuppression Therapy; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007370:Interferon Type I / Q000627:therapeutic use*; D004915:Leukemia, Erythroblastic, Acute / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D008099:Liver / Q000382:microbiology / Q000473:pathology; D051379:Mice; D009362:Neoplasm Metastasis / Q000473:pathology / Q000503:physiopathology*; D011863:Radioimmunoassay; D013154:Spleen / Q000382:microbiology / Q000473:pathology; D014412:Tumor Virus Infections
D000914:Antibodies, Viral; D007370:Interferon Type I