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 CD3-, CD8+ NK cells through ADCC. The onset of AK-5 regression is associated with the induction of humoral immune response and the augmentation of effector function. The mechanism of tumor cell death involves both necrosis and apoptosis. Interleukin-12, a 75-kDa heterodimeric cytokine, 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 process. Subcutaneous transplantation of AK-5 tumor induced the expression of IL-12 (p35 and p40) message by Day 6-8 in the splenocytes of syngenic rats. Similarly, analysis of serum samples from tumor-bearing animals showed the presence of circulating IL-12 around the same time. Interaction of immune cells with antibody-tagged AK-5 cells in vitro also triggered the expression of IL-12 message and protein by 3 hr. The circulating IL-12 in the sera of tumor-rejecting animals, as well as rIL-12, stimulated NK cell proliferation, expression of CD16 and CD25, and the activation of NK cells function. These observations suggest that the 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 activated state, thus demonstrating an efficient mechanism for the complete regression of the tumor.
Hegde
S P
SP
Centre for Cellular and Molecular Biology, Hyderabad, India.
Bright
J J
JJ
Kausalya
S
S
Khar
A
A
D000818:Animals; D003602:Cytotoxicity, Immunologic; D005260:Female; D015870:Gene Expression; D007111:Immunity, Cellular; D018664:Interleukin-12 / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D012333:RNA, Messenger; D018664:Interleukin-12