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(Circulation. 2004;109:1230-1235.)
© 2004 American Heart Association, Inc.

Clinical Investigation and Reports

Heat-Shock Protein 60-Reactive CD4⁺CD28^null T Cells in Patients With Acute Coronary Syndromes

Behnam Zal, PhD; Juan Carlos Kaski, MD, DSc, FRCP; Gavin Arno, BSc; Julius P. Akiyu, MSc; Qingbo Xu, MD, PhD; Della Cole, BSc; Michael Whelan, PhD; Nick Russell, PhD; J. Alejandro Madrigal, MD, PhD, MRCPath; I. Anthony Dodi, PhD; Christina Baboonian, PhD

From Cardiological Sciences (B.Z., J.C.K., G.A., J.P.A., Q.X., D.C., C.B.) and Onyvax Ltd (M.W., N.R.), St George’s Hospital Medical School, and the Anthony Nolan Research Institute (J.A.M., I.A.D.), Royal Free and University College London, London, UK.

Correspondence to C. Baboonian, Cardiological Sciences, St George’s Hospital Medical School, Cranmer Terrace, London SW170RE, UK. E-mail cbabooni{at}sghms.ac.uk

Received February 4, 2003; de novo received September 16, 2003; revision received December 8, 2003; accepted December 10, 2003.

Background— CD4⁺CD28^null T cells are present in increased numbers in the peripheral blood of patients with acute coronary syndrome (ACS) compared with patients with chronic stable angina (CSA). The triggers of activation and expansion of these cells to date remain unclear.

Methods and Results— Twenty-one patients with ACS and 12 CSA patients with angiographically confirmed coronary artery disease and 9 healthy volunteers were investigated. Peripheral blood leukocytes were stimulated with human cytomegalovirus (HCMV), Chlamydia pneumoniae, human heat-shock protein 60 (hHSP60), or oxidized LDL (ox-LDL). CD4⁺CD28^null cells were separated by flow cytometry and assessed for antigen recognition using upregulation of interferon- and perforin mRNA transcription as criteria for activation. CD4⁺CD28^null cells from 12 of 21 patients with ACS reacted with hHSP60. No response was detected to HCMV, C pneumoniae, or ox-LDL. Incubation of the cells with anti-MHC class II and anti-CD4 antibodies but not anti-class I antibodies blocked antigen presentation, confirming recognition of the hHSP60 to be via the MHC class II pathway. Patients with CSA had low numbers of CD4⁺CD28^null cells. These cells were nonreactive to any of the antigens used. Circulating CD4⁺CD28^null cells were present in 5 of the 9 healthy controls. None reacted with hHSP60.

Conclusions— We have shown that hHSP60 is an antigen recognized by CD4⁺CD28^null T cells of ACS patients. Endothelial cells express hHSP60 either constitutively or under stress conditions. Circulating hHSP60-specific CD4⁺CD28^null cells may, along other inflammatory mechanisms, contribute to vascular damage in these patients.

Key Words: angina • lymphocytes • antigens

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