Augmentation by OK-432 of generation of culture-induced killer cells.

A streptococcal preparation, OK-432, injected intraperitoneally, potentiated rejection of L1210 leukemic cells in semiallogeneic BALB/c mice. This increased rejection was further enhanced by a transfer of peritoneal exudate T (PET) cells, but not of spleen cells. Spleen cells incubated in vitro for 3 or more days were as effective as PET cells in stimulating tumor rejection, and were cytotoxic in vitro as tested by a 4-hr 51Cr-release assay. This cytotoxicity was closely related to the OK-432-mediated augmentation of L1210 rejection in vivo. In vitro treatment with OK-432 of spleen cells from intact mice generated nonspecific cytotoxic cells. The cells were nonadherent to plastic, radioresistant, and of Thy-1+, Lyt-1,2-, and asialoGM1+ phenotypes, and were tentatively named OK-432-induced killer (OIK) cells. They were cytotoxic to tumor cells resistant to natural killer (NK) cells, and different from NK cells or lymphokine-activated killer cells. For their generation, macromolecular synthesis and participation of plastic-adherent cells (probably macrophages) were needed. The in vivo growth of L1210 leukemic cells could not be inhibited by simultaneous administration of PET cells primed in vivo with OK-432, of spleen cells primed in vivo with OK-432 and then cultured, or of spleen cells primed in vitro with OK-432 and then cultured (OIK cells). However, a prophylactic adoptive transfer of these cells was effective in immunocompetent mice as well as in athymic nu/nu mice, but not in mice irradiated with 400 rad. The in vivo activity was attributable mainly to Lyt-1+, -2- cells radioresistant and adherent to nylon wool, which were probably amplifier/helper T cells.