RESEARCH - Increased intraarticular IL-7 in RA stimulates cell contact-dependent activation of CD4+ T cells and macrophages

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Arthritis Rheum. 2005 Jun 2;52(6):1700-1710 [Epub ahead of print]

Increased intraarticular interleukin-7 in rheumatoid arthritis patients

stimulates cell contact-dependent activation of CD4+ T cells and

macrophages.

van Roon JA, Verweij MC, Wijk MW, s KM, Bijlsma JW, Lafeber FP.

University Medical Center Utrecht, Utrecht, The Netherlands.

OBJECTIVE: To determine the level of intraarticular expression of

interleukin-7 (IL-7) in patients with rheumatoid arthritis (RA) and to

investigate the mechanisms by which IL-7 facilitates activation of CD4+ T

cells and monocyte/macrophages in RA. METHODS: IL-7 levels were measured in

synovial fluid obtained from patients with RA and patients with

osteoarthritis (OA). Immunohistologic analysis was used to assess the

expression of IL-7 in synovial tissue from patients with RA. Proliferation

and activation markers were determined in order to measure the effect of

IL-7 on mononuclear cells, isolated CD4+ T cells, and monocyte/macrophages

from the peripheral blood and synovial fluid. Cocultures of CD4+ T cells and

monocytic cells in the absence or presence of a semipermeable membrane were

performed to assess the extent to which IL-7 induces its effects, either

contact dependently or via soluble mediators. RESULTS: IL-7 levels were

increased in synovial fluid from patients with RA compared with the levels

in synovial fluid from patients with OA. Macrophages, fibroblasts, and

endothelial cells in the joint lining tissue expressed abundant IL-7. In

vitro, synovial fluid CD4+ T cells and macrophages were hyperresponsive to

IL-7 when compared with peripheral blood cells. Furthermore, IL-7 enhanced

cell contact-dependent activation of CD4+ T cells and monocyte/macrophages.

CONCLUSION: The abundant intraarticular expression of IL-7 and the

stimulation by IL-7 of contact-dependent activation of CD4+ T cells and

monocytic cells indicate that this cytokine plays an important

proinflammatory role in RA synovitis. Further identification of IL-7-induced

pathways may improve understanding of the important interactive role of CD4+

T cells and monocytic cells in RA.

PMID: 15934068

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_uids=1\

5934068 & dopt=Abstract

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