Expression of Interleukin 12 Receptor (IL-12R) and IL-18R on CD4+ T Cells from Patients with Rheumatoid Arthritis

Tetsushi Aita, Masahiro Yamamura, Masanori Kawashima, Akira Okamoto, Mitsuhiro Iwahashi, Jiro Yamana, Hirofumi Makino

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

Objective. Interleukin 12 (IL-12) and IL-18 synergistically induce interferon-γ (IFN-γ) production by T cell infiltrates in rheumatoid arthritis (RA). To investigate this synergism, we examined the expression and regulation of IL-12 receptor (IL-12R) and IL-18R on peripheral blood (PB) and synovial tissue (ST) CD4+ T cells from patients with RA. Methods. The mRNA and cell surface expression of IL-12R and IL-18R in CD4+ T cells were determined by reverse transcriptase-polymerase chain reaction and flow cytometry, respectively. IFN-γ and IL-4 production by CD4+ T cells stimulated with phorbol myristate acetate (PMA) and calcium ionophore A23187 was measured by intracellular cytokine staining and flow cytometry. Results. Despite the negligible expression of IL-12R on fresh cells, PB CD4+ T cells from RA patients expressed higher levels of both IL-12Rβ1 and β2 subunits after stimulation with anti-CD3 antibody (Ab) than the cells of healthy controls. ST CD4+ T cells contained mRNA transcripts encoding IL-12Rβ1 and β2, and expressed detectable levels of these 2 subunits on the cell surface. Their IL-12R expression was markedly augmented by costimulation with anti-CD3 Ab and IL-18. In contrast, IL-18Rα was expressed on freshly isolated PB CD4+ T cells from RA patients and controls, and the level of expression was higher in RA. IL-18Rα+ CD4+ T cells were further increased in the ST lesion, where IL-18Rβ mRNA was constitutively detected. IL-12Rβ1 and β2 were induced mainly on IL-18Rα+ CD4+ T cells after anti-CD3 Ab stimulation. PMA and A23187-activated ST CD4+ T cells mostly expressed IL-18Rα and produced high levels of IFN-γ. Conclusion. These results indicate that IL-18R-expressing CD4+ T cells are accumulated in the ST of patients with RA, where the functional IL-12R is locally induced by stimuli such as CD3 activation and IL-18. Activation of both cytokine receptors may be necessary for the EFN-γ-dominant cytokine response.

Original languageEnglish
Pages (from-to)448-456
Number of pages9
JournalJournal of Rheumatology
Volume31
Issue number3
Publication statusPublished - Mar 2004

Keywords

  • CD4+ T cells
  • Interleukin 12 receptor
  • Interleukin 18 receptor
  • Rheumatoid arthritis
  • Th1 cells

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology

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