- Volume 13 Issue 2
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Tumor Cell Clone Expressing the Membrane-bound Form of IL-12p35 Subunit Stimulates Antitumor Immune Responses Dominated by
$CD8^+$ T Cells
- Lim, Hoyong (Department of Biochemistry, College of Natural Sciences, Chungnam National University) ;
- Do, Seon Ah (Department of Biochemistry, College of Natural Sciences, Chungnam National University) ;
- Park, Sang Min (Department of Biochemistry, College of Natural Sciences, Chungnam National University) ;
- Kim, Young Sang (Department of Biochemistry, College of Natural Sciences, Chungnam National University)
- Received : 2013.02.21
- Accepted : 2013.03.11
- Published : 2013.04.30
IL-12 is a secretory heterodimeric cytokine composed of p35 and p40 subunits. IL-12 p35 and p40 subunits are sometimes produced as monomers or homodimers. IL-12 is also produced as a membrane-bound form in some cases. In this study, we hypothesized that the membrane-bound form of IL-12 subunits may function as a costimulatory signal for selective activation of TAA-specific CTL through direct priming without involving antigen presenting cells and helper T cells. MethA fibrosarcoma cells were transfected with expression vectors of membrane-bound form of IL-12p35 (mbIL-12p35) or IL-12p40 subunit (mbIL-12p40) and were selected under G418-containing medium. The tumor cell clones were analyzed for the expression of mbIL-12p35 or p40 subunit and for their stimulatory effects on macrophages. The responsible T-cell subpopulation for antitumor activity of mbIL-12p35 expressing tumor clone was also analyzed in T cell subset-depleted mice. Expression of transfected membranebound form of IL-12 subunits was stable during more than 3 months of in vitro culture, and the chimeric molecules were not released into culture supernatants. Neither the mbIL-12p35-expressing tumor clones nor mbIL-12p40-expressing tumor clones activated macrophages to secrete TNF-
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