Stephen Thompson

Main focus of research is that of immune regulation by heat shock proteins (stress proteins) in inflammatory disorders (mainly rheumatoid arthritis, inflammatory bowel disease and cardiovascular disease).

Modulation of inflammatory arthritis with the stress proteins HSP60 and BiP.
Antigen-specific CD4+ T cells appear to be a central component in the pathogenesis of a variety of human autoimmune diseases and animal models of autoimmunity. Such T cells can home to the target tissue where autoantigen is present and, after local activation, produce pro-inflammatory cytokines. These events lead to the recruitment and activation of both lymphocytes and monocytes that ultimately destroy the target tissue. Consequently, a search for antigens which could initiate and/or perpetuate T cell responses in arthritic joints is continuing. The characterisation of target antigens in autoimmune diseases is an important step towards understanding the aetiology of this group of conditions, and in designing specific immunotherapeutic regimes. Two such antigens identified in separate studies are the 60kD heat shock protein (hsp60) and the 70kD stress protein BiP. Surprisingly, immune responses to both these proteins are not pro-inflammatory but are instead classified as anti-inflammatory or regulatory. Hence continuing studies aim to utilise their regulatory potential to develop novel immunotherapeutic interventions in inflammatory diseases such as rheumatoid arthritis

Circulating cell stress proteins, leukocyte function and cardiovascular disease
There is growing evidence for the hypothesis that plasma levels of extracellular molecular chaperones, such as Hsp60 or Hsp70 correlate (positively or negatively) with susceptibility to coronary heart disease and stroke. The biological consequences of having high blood levels of such proteins are unknown. Nor have associations with subclinical coronary artery disease and risk of clinical cardiac events been established. Recent evidence has revealed that human lymphocytes are exquisitely sensitive to certain molecular chaperones with both activation and inhibition of cell function being found in vitro. The hypothesis being tested is that individuals with high levels of molecular chaperones in their circulation will evoke changes in lymphocyte function that may predispose to organ, particularly cardiovascular, pathology. This is being tested in studies combining molecular biological, immunological and epidemiological methods with cardiac imaging in a subset of the Whitehall II epidemiological cohort (a large group of civil servants who have had the development of any heart disease monitored over the past 15-20 years).