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 beta chain and gamma 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.
Cooper
S M
SM
Division of Rheumatology and Clinical Immunology, University of Vermont College of Medicine, Burlington 05405.
Dier
D L
DL
Roessner
K D
KD
Budd
R C
RC
Nicklas
J A
JA
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000473:pathology*; D002455:Cell Division; D002999:Clone Cells; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000032:analysis*; D013583:Synovial Membrane / Q000473:pathology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*
D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell