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(CD122) and 
(CD132) Chains Are Expressed by Fibroblast-Like Synoviocytes: Activation by IL-2 Stimulates Monocyte Chemoattractant Protein-1 Production1
Department of Rheumatology, Guy’s, King’s, and St. Thomas’s School of Medicine, Guy’s Hospital, London, United Kingdom
The expression of the IL-2R 
-, 
-, and 
-chains, CD25,
CD122, and CD132, respectively, was investigated on fibroblast-like
synoviocytes (FLS) and dermal fibroblasts (DF). Both protein and mRNA
for CD122 and CD132 were observed but there was no evidence of CD25
expression. Quantification of the Ag binding sites for CD122 showed
that FLS expressed 4 times more receptor molecules than DF. The
functional capability of these receptors was confirmed by the
production of monocyte chemoattractant protein-1 (MCP-1) in direct
response to stimulation by IL-2, which could be inhibited by
neutralizing anti-CD122 mAb. Both rheumatoid arthritis (RA) and
osteoarthritis (OA) FLS and DF spontaneously produced MCP-1 in culture
over a similar range of concentrations. However, RA and OA FLS produced
significantly greater levels of MCP-1 following stimulation by IL-2 and
IL-1; RA FLS produced significantly more MCP-1 than OA FLS. Addition
of exogenous IL-2 caused a slight, but significant, decrease in MCP-1
production by DF. The addition of neutralizing anti-CD122 mAb to
FLS cultures partially, but significantly, reduced the IL-2-induced
MCP-1 secretion, but did not effect either the spontaneous or
IL-1-induced secretion of MCP-1. Increased tyrosine phosphorylation
was observed in FLS lysates following 30-min incubation with IL-2. In
conclusion, in the inflamed synovium, as activated T cells migrate
through the sublining and lining layer, T cell-derived IL-2
may activate FLS to secrete MCP-1, thus recruiting macrophages into the
rheumatoid synovium and perpetuating
inflammation.
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