Resistance to apoptosis and elevated expression of bcl-2 in clonally expanded CD4+CD28- T cells from rheumatoid arthritis patients

Michael Schirmer, Abbe N. Vallejo, Cornelia M. Weyand, Jörg J. Goronzy

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160 Scopus citations


Patients with rheumatoid arthritis have a subset of CD4+ T lymphocytes that are characterized by a defect in CD28 expression. CD4+CD28- T cells frequently undergo clonal expansion in vivo. These clonotypes include autoreactive cells and persist over many years. The clonogenic potential and longevity of these T cells could be related to an altered response to apoptosis-inducing signals. To explore this possibility, CD4+CD28- T cell lines and clones were examined for their response pattern to stimuli inducing physiologic cell death. CD4+CD28- T cells were found to be resistant to apoptosis upon withdrawal of the growth factor, IL-2. To examine whether the altered sensitivity to this apoptotic signal was correlated with the expression of proteins of the bcl-2 family, the expression of bcl-2, bcl-x, and bax proteins was determined, CD28+ and CD28-CD4+ T cells could not be distinguished by the levels of bax or bcl-x(L) protein; however, CD4+CD28- T cells expressed higher amounts of bcl-2 protein than did CD4+CD28+ T cells, The increased bcl-2 expression in CD4+CD28- T cells was relatively independent of signals provided by exogenous IL-2. In CD28-deficient CD4+ T cells, bcl-2 was not significantly up-regulated by the addition of exogenous IL-2 and was maintained despite IL-2 withdrawal, as opposed to CD28- expressing CD4+ T cells. We propose that CD4+CD28- T cells are characterized by a dysregulation of the survival protein, bcl-2, which may favor the clonal outgrowth of autoreactive T cells and thus contribute to the pathogenesis of rheumatoid arthritis.

Original languageEnglish (US)
Pages (from-to)1018-1025
Number of pages8
JournalJournal of Immunology
Issue number2
StatePublished - Jul 15 1998

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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