Cartilage-reactive T cells in rheumatoid synovium

Rheumatoid arthritis (RA) is an inflammatory polyarthritis genetically linked to HLA-DR4 and related haplotypes. RA synovial tissue is characterized by T cell infiltration and activation of macrophage-like cells, strongly implicating a T cell-antigen-presenting cell (APC) interaction in RA pathogenesis. To investigate the nature of the antigens driving the T cell response, synovial tissue was obtained from a patient with chronic RA and T cells were enriched. These T cells were stimulated by endogenous APC from the same synovial tissue. The T cell lines were subsequently evaluated for responsiveness to autologous APC and cartilage antigens. Specific proliferative responses to autologous APC which were enhanced by cartilage extract were seen. Immunomagnetic bead selection and RT-PCR was used to identify TCR alphabeta pairs which appeared to respond to antigen(s) in the cartilage extract. T cell clones derived from the same joint were shown to release IL-2 in response to the cartilage extract and expressed a related TCR. With these experiments we have shown direct evidence that autoreactive T cells are found within the inflamed rheumatoid synovium and, further, that the antigens driving these T cells are cartilage derived. Since the antigens recognized by these populations of T cells are found within cartilage our data provides evidence that RA pathology could be related to a self-driven autoimmune response to cartilage proteins.