Immune Reactions Against Heat Shock Proteins and Arthritis

During the last decade our insight into the aetiology and pathogenesis of supposedly autoimmune diseases like rheumatoid arthritis made considerable progress: they seem to be helper T lymphocyte (T cell) mediated; possible triggering and/or target antigens have been identified and aberrant expression of human leucocyte antigens (products of the HLA system, the human major histocompatibility complex) may be involved in the presentation of these antigens to helper T cells. The helper T cell, which is a class II-restricted CD4 positive T cell, plays a central role in orchestrating the immune response. The way it does so is by producing cytokines or lymphokines, which regulate, at least, all the other activated (by antigen) players of the immune system. Thus the most specific and efficient immunotherapy for an autoimmune disease is to shut off the button that specifically turns on the autoreactive helper T cell. That button is the HLA molecule presenting an autoantigen to the T cell receptor of an autoreactive helper T cell. How this button for autoreactive helper T cells (Th) may indeed be turned off very efficiently, has been shown in experimental animal models and has been further discussed in the previous chapter by Kingsley and Panayi on Immunotherapy. One such animal model that has stimulated a lot of research in this direction has been adjuvant arthritis (AA), which is induced in susceptible animals (Lewis rats) by the injection of Mycobacterium tuberculosis in oil. In this model, helper T cells from affected Lewis rats have been isolated that are capable of transferring the disease to naive animals. These T cells recognize epitopes on a mycobacterial heat shock protein of 65 kDa (hsp65). In this chapter we will review the studies performed in the last 6 or 7 years, that have addressed the possible role of heat shock proteins, and in particular hsp65, in the pathogenesis of, respectively, reactive and rheumatoid arthritis.