The secreted form of p28 subunit of interleukin (IL)-27 inhibits biological functions of IL-27 and suppresses anti-allogeneic immune responses

Immunology. 2009 Sep;128(1 Suppl):e816-25. doi: 10.1111/j.1365-2567.2009.03088.x. Epub 2009 Mar 23.


Interleukin-27 (IL-27) is a new IL-12-related heterodimeric cytokine comprising a novel p28 molecule and the Epstein-Barr-virus-induced gene 3 (EBI3) molecules. It augments initiation of T helper type 1-mediated immunity by enhancing the proliferation and cytokine production of T cells. In this study, we examined whether a secreted form of IL-27 subunits would inhibit IL-27-mediated immunological responses. COS-7 cells transduced with the mouse (m) p28 gene secreted a monomeric mp28 protein; however, those transduced with the mEBI3 gene did not detect a mEBI3 protein in the culture supernatants. The secreted mp28 prevented the IL-27-mediated signal transduction and activator of transcription 1 phosphorylation and subsequently inhibited the IL-27-mediated intercellular adhesion molecule-1 induction and interferon-gamma production in CD4(+) T cells. We generated mp28-expressing murine carcinoma Colon 26 cells and inoculated a mixture of the mp28- and mIL-27-expressing Colon 26 cells into syngeneic BALB/c mice. Simultaneous production of mp28 and mIL-27 from Colon 26 cells suppressed IL-27-mediated anti-tumour effects in the mice. We examined the p28-mediated immune suppression by inoculating mp28-expressing myoblasts into allogeneic mice. Forced production of mp28 suppressed the allogeneic cytotoxic T-lymphocyte induction and subsequently retarded the graft rejection. Furthermore, production of both mp28 and mp40, which inhibits the functions of IL-12 and IL-23, prolonged the graft survival longer than the grafts expressing either mp28 or mp40. We propose that p28 can be a regulatory subunit for IL-27-mediated cellular immune responses and a possible therapeutic agent to suppress unfavourable immune responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology*
  • COS Cells
  • Cell Adhesion Molecules / agonists
  • Cell Adhesion Molecules / immunology
  • Cell Adhesion Molecules / metabolism
  • Cell Line, Tumor
  • Chlorocebus aethiops
  • Female
  • Graft Survival / immunology*
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / drug effects
  • Interferon-gamma / immunology
  • Interleukin-17 / genetics
  • Interleukin-17 / immunology*
  • Interleukin-17 / pharmacology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Minor Histocompatibility Antigens
  • Myoblasts / immunology
  • Myoblasts / metabolism
  • Neoplasms / immunology*
  • Phosphorylation
  • Protein Subunits / genetics
  • Protein Subunits / immunology
  • Protein Subunits / pharmacology
  • Receptors, Cytokine / genetics
  • Receptors, Cytokine / immunology
  • Receptors, Interleukin-12 / agonists
  • Receptors, Interleukin-12 / immunology
  • Receptors, Interleukin-12 / metabolism
  • STAT1 Transcription Factor / agonists
  • STAT1 Transcription Factor / immunology
  • STAT1 Transcription Factor / metabolism
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / metabolism
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Transduction, Genetic


  • Cell Adhesion Molecules
  • Ebi3 protein, mouse
  • Interleukin-17
  • Minor Histocompatibility Antigens
  • Protein Subunits
  • Receptors, Cytokine
  • Receptors, Interleukin-12
  • STAT1 Transcription Factor
  • Stat1 protein, mouse
  • Interferon-gamma