Generation of specific antitumor cytotoxic T-lymphocytes in monoculture can be inhibited by T-suppressors from tumor-bearing mice.

A new model for the generation of specific antitumor cytotoxic T lymphocytes (CTL) was proposed. In contrast to other models, it allows to generate secondary effector CTL (CTL-2) without tumor stimulator cells in vitro (in monoculture). C57BL/10 mice or/and C57BL/6 mice were immunized by injection with gamma-irradiated syngeneic tumor cells into the footpads. For estimation of cytotoxic activity, chromium-51 release assay was used. It has been shown that effector CTL were absent in the lymph nodes after 1-fold as well as 2-fold immunization. Cytotoxic cells have not been found in 1-fold immunization even after maturation of the lymphocytes in monoculture. Specific CTL were detected only after secondary immunization and subsequent cultivation in vitro. Effector cells had Thy1.2, CD8+, CD4- phenotype. Presence in vitro of exogenous recombinant interleukin 2 (rIL-2) was needed for the generation of CTL-2 against Mech-11 sarcoma but not against EL4 lymphoma. The spleen cells from B10 mice with progressively growing Mech-11 tumor specifically suppressed the maturation of CTL-2 against Mech-11 in monoculture. Since suppression took place in the presence of exogenous rIL2 in monoculture, it was suggested that suppression was not resulted by negative influence of the suppressor cells upon endogenic IL-2 production. The treatment of the suppressor cells with monoclonal antibody (Mab) against Thy1.2 as well as against CD4 or CD8 markers plus complement (C') considerably decreased Ts activity. Obviously, two distinct subsets of T-lymphocytes were required for suppression.