Pathophysiological functions of CD30+ CD4+ T cells in rheumatoid arthritis.
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-gamma. 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-kappaB 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.
Okamoto
Akira
A
Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine and Dentistry, Okayama 700-8558, Japan.
Yamamura
Masahiro
M
Iwahashi
Mitsuhiro
M
Aita
Tetsushi
T
Ueno
Akiko
A
Kawashima
Masanori
M
Yamana
Jiro
J
Kagawa
Hidetoshi
H
Makino
Hirofumi
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000503:physiopathology*; D015704:CD4 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002455:Cell Division / Q000276:immunology; D005260:Female; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D015847:Interleukin-4 / Q000378:metabolism; D017730:Ki-1 Antigen / Q000097:blood* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D012995:Solubility; D013583:Synovial Membrane / Q000166:cytology / Q000276:immunology / Q000378:metabolism
D015704:CD4 Antigens; D017730:Ki-1 Antigen; D016328:NF-kappa B; D015847:Interleukin-4