Unusual CD4+CD28null T Lymphocytes and Recurrence of Acute Coronary Events

Giovanna Liuzzo, Luigi M. Biasucci, Graziana Trotta, Salvatore Brugaletta, Michela Pinnelli, Giovanna Digianuario, Vittoria Rizzello, Antonio G. Rebuzzi, Carlo Rumi, Attilio Maseri, Filippo Crea

Research output: Contribution to journalArticlepeer-review


Objectives: 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.

Original languageEnglish
Pages (from-to)1450-1458
Number of pages9
JournalJournal of the American College of Cardiology
Issue number15
Publication statusPublished - Oct 9 2007

ASJC Scopus subject areas

  • Nursing(all)


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