Immunosenescence, autoimmunity, and rheumatoid arthritis

Cornelia M. Weyand, James W. Fulbright, Jörg J. Goronzy

Research output: Contribution to journalReview articlepeer-review

115 Scopus citations

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 languageEnglish (US)
Pages (from-to)833-841
Number of pages9
JournalExperimental Gerontology
Volume38
Issue number8
DOIs
StatePublished - 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

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