VARIANT MOUSE LYMPHOMA-CELLS WITH MODIFIED RESPONSE TO INTERFERON DEMONSTRATE ENHANCED IMMUNOGENICITY

We have previously developed an experimental model for the xenogenizat ion of malignant lymphoma. From highly tumorigenic S49 mouse lymphoma cells that proliferate in suspension culture (designated T-25), we sel ected variant clones that grew as an adherent monolayer (designated T- 25-Adh) and were non-tumorigenic in syngeneic mice. Furthermore, primi ng of syngeneic hosts with T-25-Adh cells protected them against subse quent challenges with the tumorigenic T-25 cells. Several lines of evi dence have indicated that antigens of an endogenous mouse mammary tumo r virus (MMTV) are involved in the immunogenicity of T-25-Adh cells. S ince interferon (IFN) is known to affect retroviral assembly and matur ation on the cell membrane, we have studied the effects of IFN on endo genous MMTV-related structures, as well as on the immunogenicity of T- 25-Adh cells. We observed that mouse alpha and beta interferons affect the morphogenesis of intracellular MMTV-related precursors in the imm unogenic T-25-Adh cells, but not in tumorigenic T-25 cells. From T-25- Adh cells we selected variants that were either high responders or low responders to the above-mentioned interferon effect. The high-respons e variants were significantly more protective against tumorigenic T-25 cells than the low-response variants. Involvement of MMTV-related ant igens in the immune response of the host to T-25-Adh cells was further suggested by immunoelectron-microscopical analysis, demonstrating tha t antisera from mice, immunized with T-25-Adh cells, interacted specif ically with cell-surface MMTV budding particles. These findings indica te a novel method for xenogenization of lymphoma cells by IFN. Since e ndogenous retroviruses are present in all tissues of the mouse, this a pproach might be applicable to a wide variety of tumors.