Molecular mechanisms involved in human autoimmune diseases: relevance of chronic antigen presentation. Class II expression and cytokine production.
The observation that the local site of autoimmune responses over-expressed HLA class II led to the formulation that tissue antigen-presenting capacity contributes significantly to the mechanism of autoimmune disease perpetuation, by continually reactivating auto-antigen-reactive T lymphocytes. These in turn produce mediator molecules which maintain HLA class II expression (and hence antigen-presenting capacity) in the target tissues; and also initiate the immune and inflammatory pathways. The importance of this concept is that it provides a readily testable hypothesis that has been investigated extensively. For the thyroid diseases compelling data to support it have accumulated; in other diseases such as rheumatoid arthritis the evidence is increasing. The concept also relates the human autoimmune diseases to the normal mechanisms of immune induction and immunoregulation. This highlights the areas that we do not yet understand, namely the interplay of genetic susceptibility, extrinsic agents or disorders of immune regulation which permit the autoimmune process to become sufficiently pronounced as to engender a clinical autoimmune disease. Even with our limited understanding of the disease process, it is apparent that there are many opportunities for newer approaches at therapy, based on interfering with the immune cells or their mediators.
Feldmann
M
M
Charing Cross Sunley Research Centre, Hammersmith, London, U.K.
D000938:Antigen-Presenting Cells / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology*; D001685:Biological Factors / Q000276:immunology*; D016207:Cytokines; D006681:HLA-D Antigens / Q000276:immunology*; D006801:Humans
D001685:Biological Factors; D016207:Cytokines; D006681:HLA-D Antigens