Perturbation of the T-cell repertoire in patients with unstable angina.
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.
Liuzzo
G
G
Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Kopecky
S L
SL
Frye
R L
RL
O'Fallon
W M
WM
Maseri
A
A
Goronzy
J J
JJ
Weyand
C M
CM
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*
D018106:CD28 Antigens; D015704:CD4 Antigens; D007371:Interferon-gamma