A viral epitope that mimics a self antigen can accelerate but not initiate autoimmune diabetes
Urs Christen, … , Michael B.A. Oldstone, Matthias G. von Herrath
Urs Christen, … , Michael B.A. Oldstone, Matthias G. von Herrath
Published November 1, 2004
Citation Information: J Clin Invest. 2004;114(9):1290-1298. https://doi.org/10.1172/JCI22557.
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Article Autoimmunity

A viral epitope that mimics a self antigen can accelerate but not initiate autoimmune diabetes

Abstract

We document here that infection of prediabetic mice with a virus expressing an H-2Kb–restricted mimic ligand to a self epitope present on β 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.

Authors

Urs Christen, Kurt H. Edelmann, Dorian B. McGavern, Tom Wolfe, Bryan Coon, Meghann K. Teague, Stephen D. Miller, Michael B.A. Oldstone, Matthias G. von Herrath

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Figure 3

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Sequential infection with LCMV and PV results in accumulation of PV-NP20...
Sequential infection with LCMV and PV results in accumulation of PV-NP205–specific CD8 T cells in the islets of Langerhans. (A) RIP-NP mice were infected with 105 PFU LCMV. After 4 weeks, one group of mice received a secondary infection of PV (105 PFU, i.p.). Left panels, pancreata were harvested at week 3 after secondary infection and 6-μm tissue sections were stained for cellular infiltration with a monoclonal antibody against CD8. Sections were counterstained with hematoxylin. Right panels, pancreata were harvested at day 5 after secondary infection and 6-μm tissue sections were cut and were stained for CD8 T cells with rhodamine X–conjugated anti-CD8 (red) and for PV-NP205–specific CD8 T cells with allophycocyanin-conjugated H-2Kb–PV-NP205 tetramers (green). Note that only after sequential infection with LCMV followed by PV are PV-NP205–specific CD8 T lymphocytes (yellow) found in the islets of Langerhans. Original magnification, ×20. (B) Expansion of PV-NP205–specific CD8 T cell populations in blood and pancreatic lymph nodes after secondary PV infection. Upper panels, flow cytometry of PV-NP205–specific CD8 T cells in the blood of LCMV-immune mice that did or did not receive secondary infection with PV, as detected by H-2Kb–PV-NP205 tetramers; mean frequencies are indicated in boxed areas. Lower panel, frequencies of PV-NP205–specific CD8 T cells were determined by flow cytometry using H-2Kb–PV-NP205 tetramer staining and by ICCS for IFN-γ expression after 5 hours of in vitro stimulation with PV-NP205 peptide.