DETECTION OF ACTIVATED T-CELL PRODUCTS IN THE RHEUMATOID JOINT USING CDNA PROBES TO INTERLEUKIN-2 (IL-2) IL-2 RECEPTOR AND IFN-GAMMA

  • 1 February 1988
    • journal article
    • research article
    • Vol. 71  (2) , 295-301
Abstract
Attempts to detect immune mediators in RA synovial fluids by bioassay or radioimmunoassay have yielded conflicting results, and so we have begun to analyse the complex immunological reactions occurring within the rheumatoid joint using recombinant DNA technology. High levels of Interleukin-2 (IL-2) and IL-2 receptor transcripts were found in the mononuclear cells of the rheumatoid lesions. Interferon.gamma. (IFN.gamma.) mRNA was also detected, although at lower level than IL-2. To investigate the possible relevance of IL-2 and IL-2 receptor mRNA expression to the chronicity of the disease, RA joint cells were cultured in the absence of any stimulus, and the duration of mRNA expression compared to that of blood mononuclear cells (PBM), optimally stimulated. IL-2 mRNA was found to persist in culture for many days, in contrast to its transient (<24 h) presence in stimulated PBM. IL-2 receptor expression was also prolonged. In contrast IFN.gamma. mRNA, present at biopsy in 10/12 RA samples, was found to increase significantly in vitro. These results suggest that persistent T cell activation is of importance in the pathogenesis of RA, and suggest that prolonged mediator production (IL-2 and IFN.gamma.) may be of importance. The elevation of IFN.gamma. mRNA in culture and its lower relative expression suggests that there are inhibitory immunoregulatory influences within the RA joint. To determine whether abnormal IL-2 mRNA expression may be due to a genetic defect in the region controlling IL-2 gene expression, Southern blotting analysis of genomic DNA was performed with a 5'' flanking probe using normal, RA and systemic lupus erythematosis patients. No abnormalities were detected.