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Autoimmune Diseases
Volume 2012 (2012), Article ID 617213, 6 pages
Review Article

The Immunosuppressive Activity of Heat Shock Protein 70

1Haematological Sciences, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE2 4HH, UK
2Department of Biochemistry, Medical Sciences Building, University of Toronto, 1 King's College Circle, Toronto, ON, Canada M5S 1A8

Received 11 June 2012; Revised 23 October 2012; Accepted 19 November 2012

Academic Editor: Fabiana Geraci

Copyright © 2012 Pawel Stocki and Anne M. Dickinson. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Heat shock protein 70 (HSP70) has previously been described as a potent antitumour vaccine. The mechanism relied on the ability of tumour derived HSP70 to associate with antigenic peptides, which, when cross presented, elicited a T cell mediated antitumour response. Subsequently, HSP70 was incorrectly described as a potent adjuvant of innate immunity, and although mistakes in the experimental approaches were exposed and associated with endotoxin contamination in the recombinant HSP70 specimen, questions still remain regarding this matter. Here we review only publications that have cautiously addressed the endotoxin contamination problem in HSP70 in order to reveal the real immunological function of the protein. Accordingly, “endotoxin free” HSP70 stimulates macrophages and delivers antigenic peptides to APCs, which effectively prime T cells mediating an antitumour reaction. Conversely, HSP70 has potent anti-inflammatory functions as follows: regulating T cell responses, reducing stimulatory capacity of DCs, and inducing development of immunosuppressive regulatory T cells. These activities were further associated with the immune evasive mechanism of tumours and implicated in the modulation of immune reactivity in autoimmune diseases and transplant-related clinical conditions. Consequently, the role of HSP70 in immune regulation is newly emerging and contrary to what was previously anticipated.