Perturbation of the T-cell repertoire in patients with unstable angina

Giovanna Liuzzo, Stephen L. Kopecky, Robert L. Frye, W. Michael O'Fallon, Attilio Maseri, Jorg J. Goronzy, Cornelia M. Weyand

Research output: Contribution to journalArticlepeer-review

327 Scopus citations

Abstract

Background - Monocytes are constitutively activated in unstable angina (UA), resulting in the production of IL-6 and the upregulation of acute phase proteins. Underlying mechanisms are not understood. To explore whether the production of the potent monocyte activator IFN-γ is altered in UA, we compared cytokine production by T lymphocytes in patients with UA (Braunwald's class IIIB) and with stable angina (SA). Methods and Results - Peripheral blood lymphocytes were collected at the time of hospitalization and after 2 and 12 weeks. Cytokine-producing CD4+ and CD8+ T cells were quantified by 3-color flow cytometry after stimulation with phorbol myristate acetate and ionomycin. UA was associated with an increased number of CD4+ and CD8+ T cells producing IFN-γ, whereas patients with SA had higher frequencies of IL-2+ and IL-4+ CD4+ T cells. Expansion of the IFN-γ + T- cell population in UA persisted for at least 3 months. Increased production of IFN-γ in UA could be attributed to the expansion of an unusual subset of T cells, CD4+CD28(null) T cells. Conclusions - Patients with UA are characterized by a perturbation of the functional T-cell repertoire with a bias toward IFN-γ production, suggesting that monocyte activation and acute phase responses are consequences of T-cell activation. IFN-γ is produced by CD4+CD28(null) T cells, which are expanded in UA and distinctly low in SA and controls. The emergence of CD4+CD28(null) T cells may result from persistent antigenic stimulation.

Original languageEnglish (US)
Pages (from-to)2135-2139
Number of pages5
JournalCirculation
Volume100
Issue number21
DOIs
StatePublished - Nov 23 1999

Keywords

  • Angina
  • Immune system
  • Interleukins
  • Ischemia
  • Lymphocytes

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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