AK-5 TUMOR-INDUCED EXPRESSION OF INTERLEUKIN-12 - ROLE OF IL-12 IN NK-MEDIATED AK-5 REGRESSION

Spontaneous regression of AK-5, a histiocytic tumor, is mediated by CD 3(-), CD8(+) NK cells through ADCC. The onset of AK-5 regression is as sociated with the induction of humoral immune response and the augment ation of effector function. The mechanism of tumor cell death involves both necrosis and apoptosis. Interleukin-12, a 75-kDa heterodimeric c ytokine, has multiple effects on T and NK cells. We have investigated the role of IL-12 in the NK cell-mediated AK-5 tumor regression proces s. Subcutaneous transplantation of AK-5 tumor induced the expression o f IL-12 (p35 and p40) message by Day 6-8 in the splenocytes of syngeni c rats. Similarly, analysis of serum samples from tumor-bearing animal s showed the presence of circulating IL-12 around the same time. Inter action of immune cells with antibody-tagged AK-5 cells in vitro also t riggered the expression of IL-12 message and protein by 3 hr. The circ ulating IL-12 in the sera of tumor-rejecting animals, as well as rIL-1 2, stimulated NK cell proliferation, expression of CD16 and CD25, and the activation of NK cell function. These observations suggest that th e ability of the AK-5 tumor to induce the endogenous production of IL- 12 may be responsible for keeping the NK cells constantly in an activa ted state, thus demonstrating an efficient mechanism for the complete regression of the tumor. (C) 1995 Academic Press, Inc.