Mechanism of tumoricidal activity of OK-432-specific L3T4+ Lyt2- T-cells.
OK-432, a streptococcal preparation, has been used in the treatment of malignant diseases. We have found that OK-432 can act as an antigen and have established an OK-432-specific L3T4+ Lyt2- T-cell line (OK2) and a clone (OK2.21) from OK-432-immunized BALB/c mice (Iad) as antitumor effector cells. OK2 proliferated and secreted interleukin 2, but only when OK-432 was presented by Iad-positive antigen-presenting cells. Despite its helper phenotype and function, OK2 could kill OK-432-pulsed Iad-positive B-lymphoma cells. This killing was inhibited only by cold specific target cells (cold-target inhibition). OK-432 induced the cytotoxicity of OK2 as a specific antigen, not as a nonspecific immunostimulator. OK2 and OK2.21 also killed Ia-negative bystander target cells only in the presence of OK-432-pulsed Iad-positive cells (bystander killing). Double-chamber experiments suggested that the bystander killing was mediated by a short-acting soluble cytolytic factor. Finally, the OK-432-specific T-cells selectively killed tumor cells, suggesting that these T-cells play an important role in the immune surveillance against malignancy.
Ozaki
S
S
Department of Clinical Research, Utano National Hospital, Kyoto, Japan.
Suginoshita
T
T
Watanabe
T
T
Obayashi
H
H
D000818:Animals; D000950:Antigens, Ly / Q000032:analysis; D001688:Biological Products / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D005434:Flow Cytometry; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010844:Picibanil / Q000276:immunology / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D000950:Antigens, Ly; D001688:Biological Products; D010844:Picibanil