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KMID : 0923620130130020063
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Immune Network
2013 Volume.13 No. 2 p.63 ~ p.69
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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
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Lim Ho-Yong
Do Seon-Ah
Park Sang-Min
Kim Young-Sang
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Abstract
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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 membrane- bound 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-?. Growth of mbIL-12p35-expressing tumor clones was more accelerated in the CD8＋ T cell-depleted mice than in CD4＋ T cell-depleted or normal mice. These results suggest that CD8＋ T cells could be responsible for the rejection of mbIL-12p35-expressing tumor clone, which may bypass activation of antigen presenting cells and CD4＋ helper T cells.
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KEYWORD
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Membrane-bound form, Interleukin-12, p35 subunit, p40 subunit, MethA fibrosarcoma
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