Pathophysiological Functions of CD30+ CD4+ T Cells in Rheumatoid Arthritis

Akira Okamoto, Masahiro Yamamura, Mitsuhiro Iwahashi, Tetsushi Aita, Akiko Ueno, Masanori Kawashima, Jiro Yamana, Hidetoshi Kagawa, Hirofumi Makino

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

High levels of soluble CD30 (sCD30) were detected in the serum and synovial fluid of patients with rheumatoid arthritis (RA), indicating the involvement of CD30+ T cells in the pathogenesis. We investigated the induction of CD30 and its functions in CD4+ T cells from patients with established RA (disease duration ≥ 2 years). CD4+ T cells from both the peripheral blood (PB) and synovial tissue (ST) of RA patients expressed surface CD30 when stimulated with anti-CD3 antibody (Ab) and anti-CD28 Ab, but their CD30 induction was slower and weaker compared with PB CD4+ T cells of healthy controls (HC). Immunohistochemical analysis showed that only a small proportion of lymphocytes expressed CD30 in the ST (-1%). RA PB CD4+ T cells, after recovery from 6-day stimulation with anti-CD3 Ab and anti-CD28 Ab, showed in intracellular cytokine staining that CD30+ T cells could produce more interleukin-4 (IL-4) but less interferon-γ. In the culture of RA PB CD4+ T cells with anti-CD3 Ab and anti-CD28 Ab, blocking anti-CD30 Ab similarly inhibited the cell proliferation and activation of nuclear factor-κB on day 4 in RA and HC, but inhibited the apoptotic cell death on day 6 only in RA. These results indicate that despite high-level expression of sCD30, the anti-inflammatory activity of IL-4-producing CD30+ CD4+ T cells may be limited in the ST due to a poor induction of surface CD30 and a susceptibility to CD30-mediated cell death.

Original languageEnglish
Pages (from-to)267-277
Number of pages11
JournalActa medica Okayama
Volume57
Issue number6
Publication statusPublished - Dec 1 2003

Keywords

  • Apoptosis
  • CD30
  • CD4 T cells
  • Interleukin-4 (IL-4)
  • Rheumatoid arthritis (RA)

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Okamoto, A., Yamamura, M., Iwahashi, M., Aita, T., Ueno, A., Kawashima, M., Yamana, J., Kagawa, H., & Makino, H. (2003). Pathophysiological Functions of CD30+ CD4+ T Cells in Rheumatoid Arthritis. Acta medica Okayama, 57(6), 267-277.