© 1999 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Inhibition of Arteriosclerosis by T-Cell Depletion in Normocholesterolemic Rabbits Immunized With Heat Shock Protein 65
From the Institute for Biomedical Aging Research, Austrian Academy of Sciences (B.M., M.M., Q.X., G.W.), and the Institute for General and Experimental Pathology, University of Innsbruck Medical School (B.M., M.M., H.D., G.W.), Innsbruck, Austria; GBF, Department of Genexpression (M.S.), Braunschweig, Germany; and Stressgen Biotechnologies Corp (E.W.), Victoria, BC, Canada. Dr Metzler is currently at the Division of Cardiology, Department of Internal Medicine, University Hospital of Innsbruck, Innsbruck, Austria.
Correspondence to Georg Wick, MD, Institute for Biomedical Aging Research, Austrian Academy of Sciences, Rennweg 10, A-6020 Innsbruck, Austria. E-mail IBA{at}oeaw.ac.at
Abstract—Previous studies in our laboratory have shown that arteriosclerotic changes can be induced in normocholesterolemic rabbits by immunization with mycobacterial heat shock protein (hsp) 65. To further investigate the immunologic mechanisms underlying such vascular lesions, 39 male New Zealand White rabbits were treated by triple immunization with fortified Freund's complete adjuvant containing 5 mg/mL Mycobacterium tuberculosis as a source of hsp65 and simultaneous immunosuppressive therapy twice per week with either anti-CD3 monoclonal antibody (1 mg/kg) and prednisolone (1 mg/kg) or prednisolone (1 mg/kg) alone. Sixteen weeks after the first immunization the animals were killed, and as expected, severe arteriosclerotic lesions in the intima of the aortic arch were found in 9 of 10 immunized rabbits. However, only 1 of 10 rabbits immunized and immunosuppressed with the combined anti-CD3 monoclonal antibody and prednisolone treatment showed a single moderate lesion in the aorta, whereas 5 of 9 rabbits immunized and immunosuppressed by prednisolone treatment alone showed lesions, albeit mild. In conclusion, the early inflammatory stages of arteriosclerotic lesions induced by immunization with hsp65 can be inhibited by immunosuppressive therapy with anti-CD3 monoclonal antibody.
Key Words: arteriosclerosis • immunosuppression • heat shock proteins • stress proteins • lymphocytes
This article has been cited by other articles:
 |
|
 |
|
  M. Benagiano, M. M. D'Elios, A. Amedei, A. Azzurri, R. van der Zee, A. Ciervo, G. Rombola, S. Romagnani, A. Cassone, and G. Del Prete Human 60-kDa Heat Shock Protein Is a Target Autoantigen of T Cells Derived from Atherosclerotic Plaques J. Immunol., May 15, 2005; 174(10): 6509 - 6517. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Mayr, S. Kiechl, M. A. Mendall, J. Willeit, G. Wick, and Q. Xu Increased Risk of Atherosclerosis Is Confined to CagA-Positive Helicobacter pylori Strains: Prospective Results From the Bruneck Study Stroke, March 1, 2003; 34(3): 610 - 615. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Maron, G. Sukhova, A.-M. Faria, E. Hoffmann, F. Mach, P. Libby, and H. L. Weiner Mucosal Administration of Heat Shock Protein-65 Decreases Atherosclerosis and Inflammation in Aortic Arch of Low-Density Lipoprotein Receptor-Deficient Mice Circulation, September 24, 2002; 106(13): 1708 - 1715. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J C Ranford and B Henderson Chaperonins in disease: mechanisms, models, and treatments Mol. Pathol., August 1, 2002; 55(4): 209 - 213. [Abstract] [Full Text] [PDF]
|
|