Functional IL-2 receptor beta (CD122) and gamma (CD132) chains are expressed by fibroblast-like synoviocytes: activation by IL-2 stimulates monocyte chemoattractant protein-1 production.
The expression of the IL-2R alpha-, beta-, and gamma-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 beta; 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 beta-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.
Corrigall
V M
VM
Department of Rheumatology, Guy's, King's, and St. Thomas's School of Medicine, Guy's Hospital, London, United Kingdom. valerie.corrigall@kcl.ac.uk
Arastu
M
M
Khan
S
S
Shah
C
C
Fife
M
M
Smeets
T
T
Tak
P P
PP
Panayi
G S
GS
D019138:Antibodies, Blocking / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000473:pathology; D001666:Binding Sites, Antibody; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D005347:Fibroblasts / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D019085:Fluorescent Antibody Technique, Direct; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D007150:Immunohistochemistry; D007376:Interleukin-2 / Q000494:pharmacology*; D008213:Lymphocyte Activation; D010766:Phosphorylation; D012333:RNA, Messenger / Q000032:analysis; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000737:chemistry / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013583:Synovial Membrane / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D014443:Tyrosine / Q000378:metabolism
D019138:Antibodies, Blocking; D018932:Chemokine CCL2; D007106:Immune Sera; D007376:Interleukin-2; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D014443:Tyrosine