Specific and non-specific autoreactive immunity.
Most autoimmune diseases are HLA-associated which supports the notion that they are dependent upon specific immune activation of a limited set of T cell clones. Findings which imply that induction of autoimmune reactivity probably does not differ from normal immune responses are discussed. The possibility of transferring autoimmune disease using T cell clones indicates that target structures for auto-immune attack are also present in healthy individuals. In the present article, it is argued that autoimmune reactions and immunity against nominal conventional antigens in principle are effected and regulated by similar mechanisms. It is assumed that persistent tissue damage occurs if immune attack is directed against tissues that cannot be regenerated, such as in diabetes, or are only slowly reconstituted, such as in rheumatoid arthritis. Normal immune responses are regulated by various inflammatory mediators and cytokines/interleukins. The joint of patients with rheumatoid arthritis is discussed as a model for propagation of immune reactions and tissue destruction in autoimmune disease. Of the different cytokines which are present in the synovial fluid or produced by cells in the synovial tissue, most are presumed to have originated in macrophages/monocytes such as IL-1, IL-6, IL-8, TNF-alpha and TGF-beta. Even so, T cells are believed to have an important role for the continued reactivity associated with autoimmune disease. This discrepancy can be explained in different ways. T cell products might escape detection because they are short-lived, they are immediately consumed or they are produced only during short time intervals.(ABSTRACT TRUNCATED AT 250 WORDS)
Möller
E
E
Department of Immunology, Stockholm University, Sweden.
Valugerdi
M A
MA
Ridderstad
A
A
D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology; D015551:Autoimmunity; D016207:Cytokines / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D008213:Lymphocyte Activation / Q000187:drug effects; D008222:Lymphokines / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D016207:Cytokines; D006680:HLA Antigens; D008222:Lymphokines