Involvement of donor lymphoreticular cells in the rejection of B16 melanoma by allogeneic mice.

B16 melanoma maintained by in vivo passage in syngeneic (C57B1/6) mice was rejected when transplanted into H-2 incompatible BALB/c mice. However, after passage in tissue culture the tumour grew in BALB/c mice and, in the case of intraperitoneal (i.p.) inoculation, was fatal. Administration of lymphoreticular cells (resident peritoneal cells, PC) bearing C57B1/6 alloantigens at the same time as the cultured tumour prevented or greatly diminished tumour growth in BALB/c mice. This occurred when the PC were given either at the same site as the tumour or at a remote site, implying that tumour rejection involved specific sensitization of the BALB/c mice to C57B1/6 alloantigens presented on the PC. Conversely, administration of PC from a strain (C3H) with a H-2 haplotype unrelated to either the tumour or the allogeneic recipient mice diminished tumour growth when given at the same site, but had no effect when given at a remote site. This result is consistent with the involvement in sensitization of a soluble factor produced by or in response to the allogeneic PC, which is not antigen-specific, and which operates over a short range. These results indicate that, as for mouse thyroid allograft rejection (Lafferty and Woodnough, 1977), rejection of a B16 melanoma allograft was dependent on the presence of donor stimulator cells of lymphoreticular origin. The implications for the generation of immunity in syngeneic and autochthonous tumour systems are discussed.