Sensitized T lymphocytes render DBA/2 beige mice responsive to IFN alpha/beta therapy of Friend erythroleukemia visceral metastases.
Interferon alpha/beta (IFN alpha/beta) is highly effective in inhibiting the development of Friend erythroleukemia cell (FLC) visceral metastases in DBA/2 mice injected intravenously (i.v.) with FLC, but does not protect FLC-injected DBA/2 beige (bg/bg) mice. Use of IFN alpha/beta-resistance FLC indicated that IFN was acting through host mechanisms in DBA/2 mice and thus pointed to a defect in some host mechanism in bg/bg mice essential for IFN's anti-metastatic action. We undertook experiments to restore in bg/bg mice the marked anti-FLC metastatic effect of IFN alpha/beta observed in DBA/2 and +/bg mice. Adoptive transfer of spleen cells from normal syngeneic mice to IFN-treated bg/bg mice was ineffective, but the transfer of splenic T lymphocytes from FLC-immunized DBA/2 or +/bg mice markedly increased the survival time of FLC-injected bg/bg mice provided that these mice were also treated with IFN alpha/beta. Neither treatment alone resulted in an increase in survival time. As few as 1 x 10(7) immune spleen cells were effective in IFN-treated FLC-injected bg/bg mice. The T-cell immune response to FLC of bg/bg mice was diminished compared with that of +/bg mice. Likewise, only combination therapy of immune spleen cells and IFN alpha/beta resulted in an increased survival time of ESb-lymphoma-injected bg/bg mice. Our results indicate the essential participation both of T-cell-mediated immune mechanisms and of IFN alpha/beta in the inhibition of FLC visceral metastases.
Laboratory of Viral Oncology, Institut de Recherches Scientifiques sur le Cancer, Villejuif, France.
T
T
Kaido
I
I
Gresser
C
C
Maury
M T
MT
Maunoury
F
F
Vignaux
F
F
Belardelli
D000818:Animals; D005622:Friend murine leukemia virus; D007114:Immunization; D016219:Immunotherapy, Adoptive; D016898:Interferon-alpha / Q000627:therapeutic use*; D016899:Interferon-beta / Q000627:therapeutic use*; D004915:Leukemia, Erythroblastic, Acute / Q000276:immunology / Q000473:pathology* / Q000628:therapy*; D051379:Mice; D008811:Mice, Inbred DBA; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D009368:Neoplasm Transplantation; D012680:Sensitivity and Specificity; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured
D016898:Interferon-alpha; D016899:Interferon-beta