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Immune Netw. 2013 Apr;13(2):63-9. doi: 10.4110/in.2013.13.2.63. Epub 2013 Apr 30.

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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  • 1Department of Biochemistry, College of Natural Sciences, Chungnam National University, Daejeon 305-764, Korea.

Abstract

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-α. 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.

KEYWORDS:

Interleukin-12; Membrane-bound form; MethA fibrosarcoma; p35 subunit; p40 subunit

PMID:
23700396
[PubMed]
PMCID:
PMC3659257
Free PMC Article
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