SENSITIZED T-LYMPHOCYTES RENDER DBA 2 BEIGE MICE RESPONSIVE TO IFN ALPHA-THERAPY BETA-THERAPY OF FRIEND-ERYTHROLEUKEMIA VISCERAL METASTASES/

Interferon alpha/beta (IFN alpha/beta) is highly effective in inhibiti ng the development of Friend erythroleukemia cell (FLC) visceral metas tases in DBA/2 mice injected intravenously (i.v.) with FLC, but does n ot protect FLC-injected DBA/2 beige (bg/bg) mice. Use of IFN alpha/bet a-resistant FLC indicated that IFN was acting through host mechanisms in DBA/2 mice and thus pointed to a defect in some host mechanism in b g/bg mice essential for IFN's anti-metastatic action. We undertook exp eriments to restore in bg/bg mice the marked anti-FLC metastatic effec t 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-im munized DBA/2 or +/bg mice markedly increased the survival time of FLC -injected bg/bg mice provided that these mice were also treated with I FN alpha/beta. Neither treatment alone resulted in an increase in surv ival time. As few as 1 x 10(7) immune spleen cells were effective in I FN-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 r esulted in an increased survival time of ESb-lymphoma-injected bg/bg m ice. Our results indicate the essential participation both of T-cell-m ediated immune mechanisms and of IFN alpha/beta in the inhibition of F LC visceral metastases.