T cell homeostasis in patients with rheumatoid arthritis

Kerstin Koetz, Ewa Bryl, Kay Spickschen, W. Michael O'Fallon, Jörg J. Goronzy, Cornelia M. Weyand

Research output: Contribution to journalArticlepeer-review

340 Scopus citations

Abstract

The immune system is equipped with an extremely large spectrum of structurally diverse receptors to recognize all potential antigens. This fundamental principle of receptor diversity is no longer upheld in patients with rheumatoid arthritis (RA), who have a marked contraction of the T cell receptor repertoire. In this study, the ability of RA patients to produce T cells and to maintain T cell homeostasis was examined. CD4 T cells containing T cell receptor rearrangement excision circles (TREC) were substantially reduced in RA patients; TREC levels in young adult patients matched those of controls 20 years older. Increased self-replication of T cells in RA was indicated by age-inappropriate erosion of telomeres in circulating T cells with almost complete attrition of telomeric reserves in patients 20-30 yr of age. The degree of telomere loss was not related to disease duration or the use of disease-modifying medication and was most pronounced in CD4+CD45RO(null) (naive) T cells. The loss of TREC-positive T cells could be a consequence of a primary defect in peripheral T cell homeostasis. Alternatively, RA patients may have impaired thymic function with the increased turnover of peripheral T cells being a secondary compensatory event.

Original languageEnglish (US)
Pages (from-to)9203-9208
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number16
DOIs
StatePublished - Aug 1 2000

ASJC Scopus subject areas

  • General

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