title: The role of T cells in rheumatoid arthritis.
abstract: In rheumatoid arthritis (RA), T cells infiltrate into the synovial membrane where they initiate and maintain activation of macrophages and synovial fibroblasts, transforming them into tissue-destructive effector cells. The diversity of the disease process and the formation of complex lymphoid microstructures indicate that multiple T cell activation pathways are involved. This model is supported by the association of distinct disease patterns with different variants and combinations of HLA class II molecules. T cell pathology in RA, however, is not limited to the joint. Affected patients have major abnormalities in the T cell pool, with a marked contraction in T cell receptor diversity and an outgrowth of large clonal populations. Clonally expanded CD4+ T cells lose expression of the CD28 molecule and gain expression of perforin and granzyme. Consequently, the functional profile of expanded CD4(+)CD28null T cells is fundamentally changed and is shifted towards tissue-injurious capabilities. CD4(+)CD28null T cells are particularly important in patients with extra-articular manifestations of RA, where they may have a direct role in vascular injury. Understanding the mechanisms underlying the loss of T cell diversity and the emergence of pro-inflammatory CD4(+)CD28null T cell clonotypes may have implications for other autoimmune syndromes.
authors.affiliation: Division of Rheumatology, Mayo Foundation, Rochester, MN, USA. weyand.cornelia@mayo.edu
authors.forename: C M
authors.initials: CM
authors.lastname: Weyand
authors.forename: E
authors.initials: E
authors.lastname: Bryl
authors.forename: J J
authors.initials: JJ
authors.lastname: Goronzy
mesh_terms: D001172:Arthritis, Rheumatoid / Q000209:etiology* / Q000235:genetics / Q000276:immunology*; D015551:Autoimmunity; D015329:Gene Rearrangement, T-Lymphocyte; D020022:Genetic Predisposition to Disease; D006801:Humans; D018448:Models, Immunological; D013583:Synovial Membrane / Q000473:pathology; D013585:Synovitis / Q000209:etiology; D013601:T-Lymphocytes