Increased proportion of CD8+ tumor responsive T cells after immunization with tum- versus tum+ rat glioma

Previously established immunogenic (tum-) clones of an ENU (ethyl-N-nitrosourea)-induced rat glioma, N32, were compared to the original tumor concerning their capacity to induce T lymphocyte responses after in vivo immunization and in vitro restimulation of responder spleen cells in mixed lymphocyte tumor culture (MLTC) assays. Quite unexpectedly, original N32 (tum+) in vivo primed spleen cells proliferated to the same extent in vitro in response to tum+ stimulator cells as did tum- in vivo primed spleen cells. However, flow-cytometric analysis of parallel cultures showed a greatly increased proportion of CD3+CD8+ lymphocytes in the proliferating responder cell population from tum- immunized hosts, contrary to a CD3+CD4+ lymphocyte dominance after tum+ immunization. Although the original tum+ N32 tumor cells are not capable of inducing a clearly demonstrable isograft rejection response, they induce a strong T cell response readily detectable in MLTC assays. We propose that the increased CD8+ lymphocyte proliferation could be an essential feature of the isograft rejection response induced by tum- tumor variants. Possible mechanisms of the augmented CD8+ T cell response are discussed.