title: Perturbation of the T-cell repertoire in patients with unstable angina.
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-gamma is altered in UA, we compared cytokine production by T lymphocytes in patients with UA (Braunwald's class IIIB) and with stable angina (SA).
  
  
  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-gamma, whereas patients with SA had higher frequencies of IL-2(+) and IL-4(+) CD4(+) T cells. Expansion of the IFN-gamma( +) T-cell population in UA persisted for at least 3 months. Increased production of IFN-gamma 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-gamma production, suggesting that monocyte activation and acute phase responses are consequences of T-cell activation. IFN-gamma 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.
authors.affiliation: Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: G
authors.initials: G
authors.lastname: Liuzzo
authors.forename: S L
authors.initials: SL
authors.lastname: Kopecky
authors.forename: R L
authors.initials: RL
authors.lastname: Frye
authors.forename: W M
authors.initials: WM
authors.lastname: O'Fallon
authors.forename: A
authors.initials: A
authors.lastname: Maseri
authors.forename: J J
authors.initials: JJ
authors.lastname: Goronzy
authors.forename: C M
authors.initials: CM
authors.lastname: Weyand
mesh_terms: D000328:Adult; D000368:Aged; D000789:Angina, Unstable / Q000276:immunology*; D018106:CD28 Antigens / Q000032:analysis; D015704:CD4 Antigens / Q000032:analysis; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D018106:CD28 Antigens; D015704:CD4 Antigens; D007371:Interferon-gamma