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Cartilage-reactive T cells in rheumatoid synovium
1Department of Medicine, Rheumatology Division, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
International Immunology
|April 28, 2000
Summary
Rheumatoid arthritis (RA) involves T cells responding to cartilage antigens in the synovium. This suggests RA pathology may stem from an autoimmune response to cartilage proteins.
Area of Science:
- Immunology
- Rheumatology
Background:
- Rheumatoid arthritis (RA) is an inflammatory polyarthritis linked to HLA-DR4.
- RA pathogenesis involves T cell and antigen-presenting cell (APC) interactions in synovial tissue.
Purpose of the Study:
- To investigate the specific antigens driving T cell responses in RA.
- To determine if T cells in RA synovium recognize cartilage-derived antigens.
Main Methods:
- Enrichment of T cells from RA synovial tissue.
- Stimulation of T cells with autologous APC and cartilage extract.
- Identification of T cell receptor (TCR) alphabeta pairs using immunomagnetic bead selection and RT-PCR.
- Assay of IL-2 release from T cell clones.
Main Results:
- T cell lines showed proliferative responses to autologous APC, enhanced by cartilage extract.
- Specific TCR alphabeta pairs were identified that responded to cartilage antigens.
- T cell clones released IL-2 in response to cartilage extract and expressed related TCRs.
Conclusions:
- Autoreactive T cells are present in inflamed rheumatoid synovium.
- Cartilage-derived antigens drive these autoreactive T cells.
- RA pathology may result from a self-driven autoimmune response to cartilage proteins.