JaLCDOI 10.18926/AMO/32814
FullText URL fulltext.pdf
Author Okamoto, Akira| Yamamura, Masahiro| Iwahashi, Mitsuhiro| Aita, Tetsushi| Ueno, Akiko| Kawashima, Masanori| Yamana, Jiro| Kagawa, Hidetoshi| Makino, Hirofumi|
Abstract <p>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 &#62;_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.</p>
Keywords apoptosis CD4 Tcells CD30 interleukin-4(IL=4) rheumatoid arthritis(RA)
Amo Type Article
Published Date 2003-12
Publication Title Acta Medica Okayama
Volume volume57
Issue issue6
Publisher Okayama University Medical School
Start Page 267
End Page 277
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
File Version publisher
Refereed True
PubMed ID 14726963
Web of Science KeyUT 000187556500001
JaLCDOI 10.18926/AMO/30745
FullText URL fulltext.pdf
Author Norii, Mika| Yamamura, Masahiro| Iwahashi, Mitsuhiro| Ueno, Akiko| Yamana, Jiro| Makino, Hirofumi|
Abstract <p>The inflamed synovial tissue (ST) of rheumatoid arthritis (RA) is characterized by the selective accumulation of interferon gamma-producing Th1-type CD4+ T cells. In this study, we investigated whether the predominance of Th1-type CD4+ cells in the ST lesion is mediated by their selective recruitment through Th1 cell-associated chemokine receptors CXCR3 and CCR5. The lymphocyte aggregates in the ST of RA contained a large number of CD4+ T cells, which mostly expressed both CXCR3 and CCR5, but not CCR4. In contrast, the frequencies of CD4+ and CD8+ T cells expressing CXCR3 and CCR5 in the blood were significantly decreased in RA patients, compared with healthy controls (HC), although there was no difference in the frequencies of CCR4-expressing CD4+ and CD8+ T cells between RA and HC. CXCR3, CCR5, and CCR4 expression in blood CD4 + T cells and CXCR3 expression in CD8+ T cells were increased after interleukin-15 (IL-15) stimulation. Therefore, the distribution of Th1-type CD4+ T cells into the ST from the blood in RA may be associated with the local expression of chemokines, both CXCR3 and CCR5 ligands, and IL-15 may play a role in enhancing these chemokine receptors on CD4+ T cell infiltrates.</p>
Keywords CXCR3 CCR5 CD4+ T cells interleukin-15 rheumatoid arthritis
Amo Type Article
Published Date 2006-06
Publication Title Acta Medica Okayama
Volume volume60
Issue issue3
Publisher Okayama University Medical School
Start Page 149
End Page 157
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
File Version publisher
Refereed True
PubMed ID 16838043
Web of Science KeyUT 000238503600002