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 lymph ocytes (CTL) was proposed In contrast to other models, it allows to ge nerate secondary effector CTL (CTL-2) without tumor stimulator cells i n vitro (in monoculture). C57BL/10 mice or/and C57BL/6 mice were immun ized by injection with gamma-irradiated syngeneic tumor cells into the footpads. For estimation of cytotoxic activity, chromium-51 release a ssay was used It has been shown that effector CTL were absent in the l ymph nodes after 1-fold as well as 2-fold immunization. Cytotoxic cell s 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 c ells 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 ce lls from B10 mice with progressively growing Mech-11 tumor specificall y suppressed the maturation of CTL-2 against Mech-11 in monoculture. S ince suppression took place in the presence of exogenous rIL2 in monoc ulture, 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) agai nst 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.