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  • Print publication year: 2005
  • Online publication date: August 2009

16 - Heat Shock Proteins Regulate Inflammation by Both Molecular and Network Cross-Reactivity



Heat shock proteins were initially identified as heterogeneous families of stress-induced proteins characterised by their chaperone activity [1]. Subsequently, they were identified as immunodominant antigens recognised by the host immune system following microbial infection [2] or during the course of autoimmune disease [3–6]. Recently, the role of heat shock proteins as endogenous activators of the innate and adaptive immune system has been unveiled [7]. In this chapter we discuss the relevance of heat shock proteins and their immune activities to the regulation of inflammation and autoimmune disease. We shall see that the regulatory activities of heat shock proteins on inflammation involve two types of cross-reactivity: molecular cross-reactivity exists between microbial and self-heat shock proteins and network cross-reactivity exists between different self-heat shock proteins.

Inflammation activates heat shock protein–specific T cells

Although the injection of incomplete Freund's adjuvant (IFA) to BALB/c mice induces local inflammation, Anderton and colleagues demonstrated that the injection of IFA also induces T cells reactive with the mammalian 60-kDa heat shock protein (Hsp60) [8]. These Hsp60-reactive T cells were TCRαβ+, CD4+ and major histocompatibility complex (MHC) class II-restricted [8]. Notably, Hsp60-specific cells could only be found in the local lymph nodes draining the site of IFA injection, and they were not present in distant lymph nodes. Hsp60-specific T cells are not only induced but also recruited to the site of inflammation [8].

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