Abstract
Current disease models of autoimmune syndromes, such as rheumatoid arthritis, propose that chronic inflammation is caused by 'forbidden T-cell clones' that recognize disease-inducing antigens and drive tissue-injurious immune reactions. Reappraisal of disease incidence data, however, emphasizes that rheumatoid arthritis is a syndrome of the elderly that occurs with highest likelihood in individuals in whom the processes of T-cell generation and T-cell repertoire formation are compromised. Thymic T-cell production declines rapidly with advancing age. Multiple mechanisms, including antigen-driven clonal expansion and homeostasis-driven autoproliferation of post-thymic T cells, impose replicative stress on T cells and induce the biological program of cellular senescence. T-cell immunosenescence is associated with profound changes in T-cell functional profile and leads to accumulation of CD4+ T cells that have lost CD28 but have gained killer immunoglobulin-like receptors and cytolytic capability and produce large amounts of interferon-γ. In patients with rheumatoid arthritis, T-cell immunosenescence occurs prematurely, probably due to a deficiency in the ability to generate sufficient numbers of novel T cells. We propose that autoimmunity in rheumatoid arthritis is a consequence of immunodegeneration that is associated with age-inappropriate remodeling of the T-cell pool.
Original language | English (US) |
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Pages (from-to) | 833-841 |
Number of pages | 9 |
Journal | Experimental Gerontology |
Volume | 38 |
Issue number | 8 |
DOIs | |
State | Published - Aug 1 2003 |
Keywords
- Aging
- CD4 T cells
- Cytotoxicity
- Killer immunoglobulin-like receptors
- Rheumatoid arthritis
ASJC Scopus subject areas
- Biochemistry
- Aging
- Molecular Biology
- Genetics
- Endocrinology
- Cell Biology