Unusual CD4+CD28null T lymphocytes and recurrence of acute coronary events.
OBJECTIVE
We hypothesized that the expansion of unusual T lymphocytes, CD4+CD28null T cells, might represent a key pathogenetic mechanism of recurrent instability.


BACKGROUND
Clinical presentation of acute coronary syndromes (ACS) is variable. Some patients have recurrent episodes of instability, despite optimal treatment, whereas others have a single acute event in their life. The CD4+CD28null T cells, with a functional profile that favors vascular injury, have recently been found both in peripheral blood and in unstable coronary plaques of patients with ACS.


METHODS
Peripheral blood T cells from 120 consecutive unstable angina (UA) patients were analyzed for the distribution of T-cell subsets by flow cytometry. Patients were subgrouped according to the occurrence of prior (during the 24 months before the study enrollment) and subsequent (during the 24 months of follow-up) acute coronary events. For 51 patients, the index event was the first ever (G1); 30 patients had prior events (G2); and 39 patients had further events at follow-up (death, myocardial infarction, or UA) or both before and after the index event (G3).


RESULTS
The CD4+CD28null T-cell frequency was higher in G3 than in G2 and G1 (median 9.5% [range 2.4% to 48.0%] vs. 5.1% [range 0.4% to 27.8%] and 2.3% [range 0.2% to 22.8%], respectively; p < 0.001). The expansion of these unusual T lymphocytes was higher in patients with elevated C-reactive protein levels, and it was reduced by statin therapy. On multivariate logistic regression analysis, CD4+CD28null T-cell frequency was an independent predictor of future acute coronary events (odds ratio 3.01, 95% confidence interval 1.1 to 8.25; p = 0.023).


CONCLUSIONS
A perturbation of T-cell repertoire is strongly associated with the recurrence of acute coronary events, conceivably playing a key pathogenetic role.
Liuzzo
Giovanna
G
Department of Cardiology, Catholic University, Rome, Italy. gliuzzo@hotmail.com
Biasucci
Luigi M
LM
Trotta
Graziana
G
Brugaletta
Salvatore
S
Pinnelli
Michela
M
Digianuario
Giovanna
G
Rizzello
Vittoria
V
Rebuzzi
Antonio G
AG
Rumi
Carlo
C
Maseri
Attilio
A
Crea
Filippo
F
D000368:Aged; D000789:Angina, Unstable / Q000276:immunology*; D002097:C-Reactive Protein / Q000032:analysis; D018106:CD28 Antigens / Q000276:immunology; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016015:Logistic Models; D008215:Lymphocytes, Null / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000276:immunology*; D010641:Phenotype; D011379:Prognosis; D011446:Prospective Studies; D012008:Recurrence; D018570:Risk Assessment; D013577:Syndrome; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D020107:Troponin T / Q000032:analysis
D018106:CD28 Antigens; D020107:Troponin T; D002097:C-Reactive Protein