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 r eceptor 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 neut ralizing anti-CD122 mAb, Both rheumatoid arthritis (RA) and osteoarthritis (OA) FLS and DF spontaneously produced MCP-1 in culture over a similar rang e 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 produc ed 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 significantl y, 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 ph osphorylation 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 F LS to secrete MCP-1, thus recruiting macrophages into the rheumatoid synovi um and perpetuating inflammation.