Effect of IL15 on T cell clonality in vitro and in the synovial fluid of patients with rheumatoid arthritis

Objective-Recent studies have suggested that interleukin (IL) 15 induces T cell accumulation in synovial lesions of rheumatoid arthritis (RA). This st udy aimed at determining whether this cytokine could explain in vivo T cell clonality in RA. Methods-Peripheral blood mononuclear cells (PBMC) from patients with RA wer e stimulated in vitro with IL15 or IL2. After isolation of mRNA from stimul ated cells and synovial T cells, genes coding the V-D(N)-J (CDR3) region of T cell receptor beta chains were amplified by a reverse transcriptase poly merase chain reaction. A single strand conformation polymorphism analysis w as used to detect the clonotype(s) of accumulating T cells. Nucleotide and amino acid sequencing was also performed. Results-Stimulation of PBMC with IL15 resulted in oligoclonal expansion of T cells. However, IL15 induced clones from PBMC were mostly different from the dominantly expanding T cell clones in synovial fluid. Furthermore, IL15 and IL2 responding clones were only partially identical. Conclusions-Although IL15 results in clonal accumulation of T cells, T cell clonality in rheumatoid joints could not be explained by the effect of IL1 5 alone. The results indicated the requirement of other factor(s), in addit ion to IL15, in the pathological process affecting RA joints. The results a lso suggested different responses by each T cell clone to IL15 or IL2.