Christen, U. et al. A viral epitope that mimics a self antigen can accelerate but not initiate autoimmune diabetes. J. Clin. Invest. 114, 1290-1298

Immune Regulation Lab, Department of Developmental Immunology, La Jolla Institute for Allergy and Immunology, San Diego, California 92121, USA.
Journal of Clinical Investigation (Impact Factor: 13.22). 12/2004; 114(9):1290-8. DOI: 10.1172/JCI22557
Source: PubMed


We document here that infection of prediabetic mice with a virus expressing an H-2Kb-restricted mimic ligand to a self epitope present on beta cells accelerates the development of autoimmune diabetes. Immunization with the mimic ligand expanded autoreactive T cell populations, which was followed by their trafficking to the islets, as visualized in situ by tetramer staining. In contrast, the mimic ligand did not generate sufficient autoreactive T cells in naive mice to initiate disease. Diabetes acceleration did not occur in H-2Kb-deficient mice or in mice tolerized to the mimic ligand. Thus, arenavirus-expressed mimics of self antigens accelerate a previously established autoimmune process. Sequential heterologous viral infections might therefore act in concert to precipitate clinical autoimmune disease, even if single exposure to a viral mimic does not always cause sufficient tissue destruction.

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    • "Collectively, the current body of evidence favoring a simple event of cross-reactivity between viral and self-antigen is weak (Richter et al. 1994; Horwitz et al. 1998; Schloot et al. 2001). Nevertheless, molecular mimicry has been shown to accelerate disease progression under conditions of virus-induced pancreatic inflammation, suggesting that sequence homologies may not be the initiating trigger, but are able to codetermine the pace by which disease develops (Christen et al. 2004). "
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    • "However, a second infection can, by expanding the autoreactive T cell compartment, cause autoimmunity (Welsh and Fujinami, 2007). Mice transgenic for a lymphocytic choriomeningitis virus (LCMV) nuclear protein remain healthy when infected with LCMV, but a subsequent infection with either poliovirus or vaccinia virus leads to the development of pancreatic inflammation and autoimmune diabetes(Christen et al., 2004; Evans et al., 1996). "
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