T-cell senescence and contraction of T-cell repertoire diversity - Catalysts of autoimmunity and chronic inflammation

Jörg J. Goronzy, Cornelia M. Weyand

Research output: Contribution to journalReview articlepeer-review

138 Scopus citations

Abstract

Rheumatoid arthritis (RA), like many other autoimmune syndromes, is a disease of adults, with the highest incidence rates reported in the elderly. The immune system undergoes profound changes with advancing age that are beginning to be understood and that need to be incorporated into the pathogenetic models of RA. The age-related decline in thymic function causes extensive remodeling of the T-cell system. Age-dependent changes in T-cell homeostasis are accelerated in patients with RA. The repertoire of naive and memory T cells is less diverse, possibly as a result of thymic insufficiency, and it is biased towards autoreactive cells. Presenescent T cells emerge that are resistant to apoptosis and that often expand to large clonal populations. These cells are under the regulatory control of nonconventional costimulatory molecules, display potent effector functions, and appear to be critical in the synovial and extra-articular manifestations of RA.

Original languageEnglish (US)
Pages (from-to)225-234
Number of pages10
JournalArthritis Research and Therapy
Volume5
Issue number5
StatePublished - Oct 2003

Keywords

  • Costimulation
  • Immunosenescence
  • Pathogenesis
  • Rheumatoid arthritis
  • T-cell homeostasis

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology

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