Document Detail

Heat-shock protein 60-reactive CD4+CD28null T cells in patients with acute coronary syndromes.
MedLine Citation:
PMID:  14993140     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: CD4+CD28null 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+CD28null cells were separated by flow cytometry and assessed for antigen recognition using upregulation of interferon-gamma and perforin mRNA transcription as criteria for activation. CD4+CD28null 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+CD28null cells. These cells were nonreactive to any of the antigens used. Circulating CD4+CD28null 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+CD28null T cells of ACS patients. Endothelial cells express hHSP60 either constitutively or under stress conditions. Circulating hHSP60-specific CD4+CD28null cells may, along other inflammatory mechanisms, contribute to vascular damage in these patients.
Behnam Zal; Juan Carlos Kaski; Gavin Arno; Julius P Akiyu; Qingbo Xu; Della Cole; Michael Whelan; Nick Russell; J Alejandro Madrigal; I Anthony Dodi; Christina Baboonian
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2004-03-01
Journal Detail:
Title:  Circulation     Volume:  109     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2004 Mar 
Date Detail:
Created Date:  2004-03-16     Completed Date:  2004-06-28     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1230-5     Citation Subset:  AIM; IM    
Cardiological Sciences, St George's Hospital Medical School, London, UK.
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MeSH Terms
Acute Disease
Angina Pectoris / immunology*
Antigen Presentation
Antigens, CD28 / analysis
CD4 Lymphocyte Count
CD4-Positive T-Lymphocytes / immunology*,  metabolism
Cell Separation
Chaperonin 60 / blood,  immunology*
Chlamydophila pneumoniae / immunology
Coronary Disease / immunology*
Cytomegalovirus / immunology
Flow Cytometry
HLA-D Antigens / immunology
Inflammation / immunology
Interferon-gamma / biosynthesis,  genetics
Lipoproteins, LDL / immunology
Lymphocyte Activation
Membrane Glycoproteins / biosynthesis,  genetics
Myocardial Infarction / immunology
Pore Forming Cytotoxic Proteins
RNA, Messenger / biosynthesis
T-Lymphocyte Subsets / immunology*,  metabolism
Reg. No./Substance:
0/Antigens, CD28; 0/Chaperonin 60; 0/HLA-D Antigens; 0/Lipoproteins, LDL; 0/Membrane Glycoproteins; 0/Pore Forming Cytotoxic Proteins; 0/RNA, Messenger; 0/oxidized low density lipoprotein; 126465-35-8/Perforin; 82115-62-6/Interferon-gamma

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