AK cells were developed from NK cells during in vitro culture of allogeneic or F1 anti-parental stimulation: functional conversion in recognizing H-2 expression of target cells accompanied by phenotypical conversion.

In vitro sensitization of (CBA x A)F1 spleen cells for 3 days with allogeneic C57BL cells raised the killer activity to the NK-sensitive YAC-1 target. When (A x C57BL)F1 spleen cells were cultured with parental C57BL cells, the lytic activity to YAC-1, P815 and EL-4 targets occurred on Day 6 after the culture. Phenotypical analyses showed that these culture-activated killer (AK) cells were derived from asialo-GM1+Thy-1-NK cells; however, they expressed Thy-1 antigen but not asialo-GM1 antigen at the effector cell level. Generation of the AK cells was not evident in cultures of spleen cells from mice with a neonatally induced tolerance to stimulator antigen and in those from T-cell-depleted mice. The supernatant of allostimulated culture, which contained a low concentration of IL-2, rendered the above cells capable of evoking AK activity. The H-2-reduced target cells were sensitive to NK cells, but less sensitive to AK cells; on the contrary, the H-2 highly expressed cells (interferon-treated cells) were less susceptible to NK cells but highly susceptible to AK cells. Thus, the relation between NK susceptibility and susceptibility to AK cells is inverse. Our study shows that stimulation with lymphokines causes a functional conversion accompanied by a phenotypical conversion of NK cells. With reference to immunosurveillance, these observations lead to the idea that NK and AK cells represent two functionally distinct but complementary systems involved in cell-mediated immunosurveillance.