The autoimmune pathogenesis of rheumatoid arthritis: role of autoreactive T cells and new immunotherapies.
OBJECTIVE
To review the role of T lymphocytes in the pathogenesis of rheumatoid arthritis (RA) and discuss the relevance of the components of the trimolecular complex (synovial T cells, autoantigens, and antigen presenting cells) in the pathogenic autoimmune response in RA.


METHODS
Currently available experimental data are combined into a hypothetical pathway that may explain some of the events in the RA process. The literature regarding the potential therapeutic strategies that interfere with specific components of the trimolecular complex and other mediators are discussed briefly.


RESULTS
T cells are activated in the peripheral blood, cross the endothelial cell wall, and migrate into the joints. Once in the synovial joints, T cells are reactivated by cross-reactive antigens and clonally expand. Clonally expanded T cells accumulate in the diseased joint and secrete proinflammatory cytokines that attract and activate other cells, such as monocytes and macrophages. Treatment with anti-CD4 monoclonal antibodies or anticytokine agents that prevents antigen presentation and/or T-cell activation were effective in RA. Other therapies, such as T-cell vaccination and T-cell receptor peptide vaccination targeting autoreactive T cells, showed clinical improvement, suggesting a pathogenic role of these lymphocytes in disease progression.


CONCLUSIONS
T cells appear to be actively involved in the pathogenesis of RA, but several parts of the pathway are hypothetical and further research is needed.
VanderBorght
A
A
Biomedisch Onderzoeksinstituut DWI, Limburgs Universitair Centrum, Diepenbeek, Belgium.
Geusens
P
P
Raus
J
J
Stinissen
P
P
D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000628:therapy*; D001324:Autoantigens; D015551:Autoimmunity; D006801:Humans; D007167:Immunotherapy; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis; D013583:Synovial Membrane / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*
D001324:Autoantigens; D011948:Receptors, Antigen, T-Cell