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CLINICAL RESEARCH: ACUTE CORONARY SYNDROME

Unusual CD4⁺CD28^null T Lymphocytes and Recurrence of Acute Coronary Events

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

^_* Department of Cardiology, Catholic University, Rome, Italy
Department of Flow Cytometry Core Laboratory, Catholic University, Rome, Italy
Dipartimento Cardiotoracovascolare, Università "Vita e Salute," Milan, Italy.

Manuscript received April 5, 2006; revised manuscript received May 3, 2007, accepted June 3, 2007.

^_* Reprint requests and correspondence: Dr. Giovanna Liuzzo, Cardiology, Catholic University, Largo A. Gemelli, 8-00168 Rome, Italy. (Email: gliuzzo{at}hotmail.com).

Objectives: We hypothesized that the expansion of unusual T lymphocytes, CD4⁺CD28^null 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⁺CD28^null 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⁺CD28^null 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⁺CD28^null 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.

Abbreviations and Acronyms   ACS = acute coronary syndrome   CCU = coronary care unit   CRP = C-reactive protein   CSA = chronic stable effort angina   cTnT = cardiac troponin T   IFN- = interferon-   UA = unstable angina

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