Immune Netw.  2013 Apr;13(2):63-69. 10.4110/in.2013.13.2.63.

Tumor Cell Clone Expressing the Membrane-bound Form of IL-12p35 Subunit Stimulates Antitumor Immune Responses Dominated by CD8+ T Cells

Affiliations
  • 1Department of Biochemistry, College of Natural Sciences, Chungnam National University, Daejeon 305-764, Korea. young@cnu.ac.kr

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-alpha. 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.

Keyword

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

MeSH Terms

Animals
Antigen-Presenting Cells
Clone Cells
Corynebacterium
Fibrosarcoma
Interleukin-12
Interleukin-12 Subunit p35
Interleukin-12 Subunit p40
Macrophages
Mice
Rejection (Psychology)
T-Lymphocytes
T-Lymphocytes, Helper-Inducer
Tumor Necrosis Factor-alpha
Corynebacterium
Interleukin-12
Interleukin-12 Subunit p35
Interleukin-12 Subunit p40
Tumor Necrosis Factor-alpha
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