CD4+ CD7- CD28- T cells are expanded in rheumatoid arthritis and are characterized by autoreactivity

Dorle Schmidt, Jörg J. Goronzy, Cornelia M. Weyand

Research output: Contribution to journalArticlepeer-review

390 Scopus citations

Abstract

Clonal expansion of CD4+ T cells is a characteristic finding in patients with RA and is only infrequently found in patients with psoriatic arthritis and healthy controls. Expanded CD4+ clonotypes are present in the blood, infiltrate into the joint, and persist over years. We have now addressed the question of whether the expanded clonotypes have unique functional and phenotypic properties which may explain the preferential in vivo expansion in RA. In contrast to most CD4+ T cells, expanded clonotypes lacked the expression of the CD28 and CD7 cell surface molecules. Accordingly, the subsets of CD4+ CD28- (9.7 vs. 1.7, P = 0.00002) and CD4+ CD7- T cells (21.5 vs. 12.6, P = 0.018) were increased in RA patients compared with age- matched normal individuals. Despite the lack of CD28 expression, clonally expanded CD4+ T cells were not anergic but proliferated in response to immobilized anti-CD3 and could be maintained in tissue culture. In vivo expanded CD4+ T cells were autoreactive to ubiquitously distributed autoantigens. They responded in an autologous mixed lymphocyte reaction, and T cell clones isolated from selected patients proliferated to autologous peripheral blood adherent cells. These data suggest that in RA patients selected CD4+ T cells which share the CD7- CD28- phenotype escape from peripheral tolerance.

Original languageEnglish (US)
Pages (from-to)2027-2037
Number of pages11
JournalJournal of Clinical Investigation
Volume97
Issue number9
DOIs
StatePublished - May 1 1996

Keywords

  • T cell receptor
  • T cells
  • autoimmunity
  • clonal expansion
  • rheumatoid arthritis

ASJC Scopus subject areas

  • Medicine(all)

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