Biological response modifiers (BRM) as antigens. III. T cell lines specific for BRM kill tumor cells in a BRM-specific manner.
In order to investigate tumoricidal effector cells in therapy by biological response modifiers (BRM) such as Propionibacterium acnes, bacillus Calmette-Guérin (BCG), Streptococcus pyogenes and a protein-bound polysaccharide (PSK), we established T cell lines specific for each BRM from BALB/c mice immunized with the corresponding BRM. These T cell lines proliferated and produced interleukin-2 (IL-2) and/or IL-4, but only in the presence of the relevant BRM and BALB/c spleen cells as the antigen and antigen-presenting cells respectively. Cross-functional experiments indicated that each BRM acts as a nominal antigen, but not as a non-specific immunostimulator. In addition, the T cell lines killed Ia-positive syngeneic B lymphoma cells, but only in the presence of the relevant BRM. These experiments excluded the possibility of cytotoxic effects by each BRM. The T cell lines and clones also killed Ia-negative bystander target cells, but only in the presence of both a relevant antigen and antigen-presenting cells. The T cell clones specific for S. pyogenes or P. acnes tested were Thy1+, L3T4+ and Lyt2-. These results indicate that some BRM exert tumoricidal activity by inducing T cells that recognize them as an antigen and kill tumor cells in an antigen-specific manner. The T cells killed tumor targets in either a tumor-necrosis-factor(TNF)-dependent or a TNF-independent manner. The mediator of the latter pathway remains to be elucidated.
Ozaki
S
S
Second Division of Internal Medicine, Kyoto University Faculty of Medicine, Japan.
Okazaki
T
T
Nakao
K
K
D000818:Animals; D000941:Antigens / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000633:toxicity*; D001500:BCG Vaccine / Q000276:immunology / Q000633:toxicity; D002460:Cell Line; D000939:Epitopes; D007114:Immunization; D007155:Immunologic Factors / Q000276:immunology* / Q000633:toxicity*; D016219:Immunotherapy, Adoptive; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D011425:Propionibacterium acnes / Q000276:immunology; D011509:Proteoglycans / Q000276:immunology / Q000633:toxicity; D012680:Sensitivity and Specificity; D013601:T-Lymphocytes / Q000276:immunology*
D000941:Antigens; D000951:Antigens, Neoplasm; D001500:BCG Vaccine; D000939:Epitopes; D007155:Immunologic Factors; D011509:Proteoglycans; C010770:polysaccharide-K