Phenotypic and functional characteristics of in vivo-induced interleukin-12-activated killer cells.
A single i.p. administration of IL-12 (2000 U/mouse) into the mice caused the elevation of serum IFN-gamma activity and the generation of killer cells which can lyse various kinds of tumor cells including both NK-sensitive and -resistant tumor cells. Such in vivo induced killer cells were not detected in the mice treated with the same dose of IL-2. The generation of IL-12-activated killer cells (IL-12AK) peaked at day 1 and sustained their cytotoxicity until day 3 after IL-12 administration. The generation of IL-12AK was inhibited by in vivo administration of anti-asialo GM1 (ASGM1) Ab but not anti-CD4 or anti-CD8 mAbs, suggesting that the precursor cells for IL-12AK were ASGM1+CD4-CD8- NK cells. The phenotypic characterization of in vivo induced effector cells with IL-12AK activity was carried out by separating the cells with FACStar. The IL-12AK activity was highly enriched in ASGM1+CD4-8- or NK1.1+CD4-8- NK cells, but not in CD8+ T cells and CD4+ T cells. The IL-12AK cells were also generated in tumor-inoculated mice. In parallel with the in vivo generation of IL-12AK generation, the growth of i.p. inoculated MBL-2 lymphoma cells was markedly inhibited by the administration with IL-12. The in vivo antitumor activity of IL-12 was blocked by the administration of anti-ASGM1 but not anti-CD4 or anti-CD8 mAbs in concomitant with the decrease of IL-12AK generation. From these results, it was indicated that ASGM1+NK1.1+CD4-8- NK type IL-12AK cells might play an important role in IL-12-induced local therapy of tumor in vivo.
Nishimura
T
T
Department of Immunology, Tokai University School of Medicine, Isehara, Japan.
Watanabe
K
K
Lee
U
U
Yahata
T
T
Kobayashi
M
M
Herrmann
S H
SH
Habu
S
S
D000818:Animals; D017690:Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000276:immunology; D018664:Interleukin-12 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008223:Lymphoma / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype
D018664:Interleukin-12