Unchecked CD70 expression on T cells lowers threshold for T cell activation in rheumatoid arthritis

Won Woo Lee, Zhi Zhang Yang, Guangjin Li, Cornelia M. Weyand, Jörg J. Goronzy

Research output: Contribution to journalArticlepeer-review

68 Scopus citations

Abstract

Rheumatoid arthritis (RA) is characterized by premature immune aging with accumulation of degenerate T cells deficient for CD28. Gene expression profiling of CD4+CD28- and CD4+CD28+ T cells to discover disease-promoting activities of CD28- T cells identified expression of CD70 as a most striking difference. Hence, CD70 was significantly more expressed in CD4 T cells from RA patients compared with age-matched controls (p < 0.006). The underlying mechanism was a failure to repress CD70 expression after activation-dependent induction. This defect in RA was not related to differential promoter demethylation. CD70 on bystander CD4 +CD28- T cells functioned by lowering the threshold for T cell activation; admixture of CD4+CD28- T cells augmented TCR-induced responses of autologous naive CD4+CD28+ T cells, particularly of low-avidity T cells. The data support a model in which CD70 expressed on T cells causes degeneracy in T cell responses and undermines tolerance mechanisms that normally control T cell autoreactivity.

Original languageEnglish (US)
Pages (from-to)2609-2615
Number of pages7
JournalJournal of Immunology
Volume179
Issue number4
DOIs
StatePublished - Aug 15 2007

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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