Chapter 10 : Pathogenetic Mechanisms and Therapeutic Approaches in Superantigen-Induced Experimental Autoimmune Diseases

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Pathogenetic Mechanisms and Therapeutic Approaches in Superantigen-Induced Experimental Autoimmune Diseases, Page 1 of 2

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In principle, three distinct mechanisms mediate superantigenic impact on the onset/relapse of autoimmune disease. First, superantigens may, following presentation on antigen-presenting cells, directly activate autoreactive T and B cells, which will migrate to the appropriate organ and once there contribute to tissue destruction by production of chemokines, proinflammatory cytokines, and tissue destructive proteinases. Second, innocent (i.e., nonautoreactive) bystander lymphocytes will be activated, thereby triggering nonspecific inflammatory response that might lead to disease relapse in the chronic phase of autoimmune disease. Finally, superantigens are able to activate the antigen-presenting cells, such as macrophages. Microbial superantigens encompass viral and bacterial proteins that share the ability to interact with major histocompatibility complex (MHC) class II and the T-cell receptor, thereby bypassing the conventional antigen-processing pathway. Superantigens have been implicated in several inflammatory diseases with and without autoimmune background. With these conditions one can include Kawasaki syndrome, psoriasis, rheumatoid arthritis, autoimmune myositis, and diabetes mellitus. Superantigens are able to interact with synoviocytes thereby triggering their production of chemokines (RANTES, monocyte chemoattractant protein-1 [MCP-1], and interleukin-8 [IL-8]). It has been clear for a decade that microbial superantigens have a significant impact on the expression of autoimmune and immune-mediated diseases. Indeed, depending on the timing and dose of superantigen, injecting of superantigen may affect the incidence and course of an autoimmune disease. Further studies on the therapeutic uses of superantigens as well as specific silencing of superantigen-mediated aberrant immune responses are definitely merited.

Citation: Tarkowski A. 2007. Pathogenetic Mechanisms and Therapeutic Approaches in Superantigen-Induced Experimental Autoimmune Diseases, p 159-168. In Kotb M, Fraser J (ed), Superantigens. ASM Press, Washington, DC. doi: 10.1128/9781555815844.ch10

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Immune Systems
Bacterial Proteins
Mouse mammary tumor virus
MHC Class II
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