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.
|Original language||English (US)|
|Number of pages||7|
|Journal||Archivum Immunologiae et Therapiae Experimentalis|
|State||Published - 2000|
ASJC Scopus subject areas
- Immunology and Allergy