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.