CD4 T cells represent a major component of the synovial inflammation in RA, however, T cell activation has been difficult to prove. To provide evidence for antigen specific recognition underlying RA synovitis, we have analyzed the diversity of tissue infiltrating T lymphocytes. To target a functionally relevant subpopulation of the infiltrate, CD4 IL-2R and CD4 IL-2R" T cells were isolated from synovial tissue of 14 RA patients. Within these T cell subsets, clonally proliferating specificities were identified based upon dominance of TCR transcripts by BV-BJ specific PCR, size fractionation of the amplified product, and sequencing. AH patients had a small number of clonally proliferating CD4 T cells in the joint. Based upon their distribution pattern, they could be subdivided into two types, clonally expanded CD4 T cells which were present in similar frequencies in the synovial compartment and the peripheral blood and clonally proliferating CD4 T cells which were exclusively present in the joint. 70% of the joint specific T cells were only found in the IL-2R fraction. The interpretation that these clonotypes resulted from antigen driven proliferation in the joint was emphasized by the finding that clonotypes with identical TCR βchains were isolated from distinct joints and at various timepoints in the same patient. Our data indicate that ubiquitously distributed as well as joint specific antigens are responsible for the clonal expansion of a small number of CD4 T cells within a heterogeneous synovial T cell infiltrate. Each patient utilizes a distinct set of CD4 T cells to react to joint residing antigens, suggesting that several different antigens are driving the T cell response in the joint.
|Original language||English (US)|
|Journal||Journal of Investigative Medicine|
|State||Published - 1996|
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)