Regulatory functions of hapten-reactive helper and suppressor T lymphocytes. III. Amplification of a generation of tumor-specific killer T-lymphocyte activities by suppressor T-cell-depleted hapten-reactive T lymphocytes.
2,4.6-trinitrophenyl (TNP)-reactive T-cell activities were raised in mice by immunization with TNP-isologous mouse gamma globulin. After establishing that TNP-reactive T lymphocytes can serve as amplifier cells for induction of killer T lymphocytes in allogeneic system, we explored the possibility of this hapten-reactive T-cell system to amplify tumor-specific killer T-lymphocyte activity in the syngeneic system. We utlized relatively weak immunogenic syngeneic plasmacytoma X5563 in C3H/He mice. Analysis of the TNP-reactive T-cell activities revealed that such T lymphocytes express the biological functions of both major subtypes of regulatory T cells, namely suppressors and helpers, and that TNP-reactive suppressor and helper T lymphocytes, respectively, differ in their relative susceptibility to specific inactivation by TNP conjugates of the nonimmunogenic D-amino acid copolymer, D-glutamic acid, and D-lysine (D-GL). By taking advantage of the relative susceptibility-difference to TNP-D-GL, selective inactivation of TNP-reactive suppressor T cells was induced by appropriate treatment with TNP-D-GL, and the generation of TNP-reactive helper T-cell activity was amplified. The supplement of augmented TNP-reactive helper T-cell activity to the system at the immunization with syngeneic X5563 with TNP-haptenation, resulted in a striking augmentation of induction of tumor-specific killer T-lymphocyte activity, and a considerable number of hosts survived after the challenge with lethal dose of viable tumor cells. Thus, appropriate manipulations designed to induce potent hapten-reactive helper T-lymphocytes provided the potential for a very effective mode of immunoprophylaxis against tumor.
D000818:Animals; D000951:Antigens, Neoplasm; D002352:Carrier Proteins / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D005260:Female; D006241:Haptens; D007156:Immunologic Memory / Q000528:radiation effects; D007165:Immunosuppression Therapy; D007694:Killer Cells, Natural / Q000276:immunology; D008211:Lymphocyte Cooperation / Q000528:radiation effects; D008297:Male; D051379:Mice; D009374:Neoplasms, Experimental / Q000276:immunology*; D010954:Plasmacytoma / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014965:X-Rays
D000951:Antigens, Neoplasm; D002352:Carrier Proteins; D006241:Haptens