Diversity of rheumatoid synovial tissue T cells by T cell receptor analysis. Oligoclonal expansion in interleukin‐2–responsive cells

The synovitis of rheumatoid arthritis (RA) is characterized by infiltrates of CD4+ T lymphocytes. To determine the clonal diversity of these cells, we cloned T cells with interleukin‐2 (IL‐2), alone or with phytohemagglutinin (PHA), directly from actively inflamed synovial tissue obtained at synovectomy. A total of 205 clones from 4 specimens was analyzed for T cell receptor (TCR) gene rearrangements using Hind III and Eco RI digests with β chain and γ chain complementary DNA probes. A comparison of the TCR rearrangements enabled us to determine if the T cell clones arose from the same or different precursor cells. Most of the T cell clones (92%) had distinct TCR gene rearrangement patterns, indicating a unique clonal origin. However, a few clones (1 quadruplicate and 6 pairs) with identical TCR rearrangements were identified, and these clonal multiples were most commonly found in clones selected with IL‐2 alone. Mass cultures were propagated with IL‐2, alone or with PHA, and at each passage, cells were removed for TCR analysis. The later passages of the lines selected with IL‐2 had oligoclonal TCR rearrangements, whereas no oligoclonal rearrangements were found in the PHA + IL‐2‐selected cell lines. The TCR rearrangements in the later passages of the IL‐2 mass cultures were often identical to the TCR rearrangements that were found in the IL‐2‐derived clonal multiples. These findings indicate that while the majority of CD4+ T cells within the actively inflamed rheumatoid joint have diverse clonal origins, small numbers of clonal multiples and oligoclonal populations are present, and these cells may be enriched in an IL‐2‐responsive T cell subset.