Superantigens and their role in infectious disease.
Although the exact mechanisms by which superantigens may contribute to the pathogenesis of diseases are unknown, it seems increasingly likely that they have a role in the induction and pathogenesis of disease. The studies described here demonstrate that in several different diseases either bacterial or viral superantigens can be isolated from patients. There is also a preferential expansion of particular V beta T-cell subsets, which is a common feature of superantigen stimulation. From the work that has been done to date it can be hypothesized that superantigens may act in several ways. They may stimulate and activate T cells that are autoreactive and lead to the induction or exacerbation of autoimmune disease, as in RA. Alternatively, they may lead to the depletion of T-cell subsets based on V beta expression, thereby resulting in the severe reduction in lymphocytes in certain immunodeficiency diseases such as AIDS. But perhaps the most likely contribution of superantigens to disease pathogenesis is seen indirectly by their effect on the immune system-particularly the stimulation of large numbers of T lymphocytes expressing the same V beta domain. Thus it is likely that the direct effect of various T-cell-derived inflammatory mediators (i.e., interleukins and other cytokines) released by these activated T lymphocytes is the primary cause of disease pathology via response to superantigen stimulation. In addition to the diseases discussed here, there are a number of other diseases in which a potential role for superantigens is being studied. These include autoimmune diseases seen after group A streptococcal infections in which the streptococcal M protein has been postulated to act as a superantigen such as scarlet fever, rheumatic heart disease, and poststreptococcal glomerulonephritis. Other diseases being studied include psoriasis, lupus-like disease, and lymphoproliferative diseases (reviewed in Kotzin et al.). In the coming years the exact role of superantigens and the specific mechanisms by which they contribute to disease should be more clearly defined. Our understanding of these molecules could also lead to new therapies for the treatment of these diseases.
Schafer
R
R
Department of Microbiology and Immunology, West Virginia University School of Medicine, Morgantown, USA.
Sheil
J M
JM
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology; D000818:Animals; D000942:Antigens, Bacterial / Q000502:physiology*; D000956:Antigens, Viral / Q000502:physiology*; D001168:Arthritis / Q000276:immunology; D002648:Child; D003141:Communicable Diseases / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D008324:Mammary Tumor Virus, Mouse / Q000502:physiology; D051379:Mice; D009080:Mucocutaneous Lymph Node Syndrome / Q000276:immunology; D051381:Rats; D012772:Shock, Septic / Q000276:immunology; D018089:Superantigens / Q000502:physiology*
D000942:Antigens, Bacterial; D000956:Antigens, Viral; D018089:Superantigens