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Research Article Free access | 10.1172/JCI117689

Sensitization to self (virus) antigen by in situ expression of murine interferon-gamma.

M S Lee, M von Herrath, H Reiser, M B Oldstone, and N Sarvetnick

Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037.

Find articles by Lee, M. in: PubMed | Google Scholar

Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037.

Find articles by von Herrath, M. in: PubMed | Google Scholar

Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037.

Find articles by Reiser, H. in: PubMed | Google Scholar

Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037.

Find articles by Oldstone, M. in: PubMed | Google Scholar

Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037.

Find articles by Sarvetnick, N. in: PubMed | Google Scholar

Published February 1, 1995 - More info

Published in Volume 95, Issue 2 on February 1, 1995
J Clin Invest. 1995;95(2):486–492. https://doi.org/10.1172/JCI117689.
© 1995 The American Society for Clinical Investigation
Published February 1, 1995 - Version history
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Abstract

Autoimmune disease results from inflammatory destruction of tissues by aberrant self-reactive lymphocytes. We studied the autoimmune potential of T lymphocytes immunologically ignorant of viral antigens acting as self antigens and whether the host defense molecule IFN-gamma could stimulate these cells to cytotoxic competency. For this purpose, we produced double transgenic mice expressing pancreatic IFN-gamma as well as lymphocytic choriomeningitis virus (LCMV) nucleoprotein (NP) or glycoprotein (GP) antigen. 100% of the NP+/IFN-gamma+ mice became diabetic before 2 mo of age, while none of the NP single transgenic littermates and only 10% of IFN-gamma single transgenic littermates did. Strikingly, NP+/IFN-gamma+ mice spontaneously developed cytotoxic T lymphocyte activity on LCMV-infected targets and vaccinia virus-NP-infected ones without prior LCMV infection but NP+/IFN-gamma- mice did not, which indicates specific sensitization to the viral antigen by IFN-gamma. These results suggest that lymphocytes ignorant of self antigens can be activated by IFN-gamma released after immunologic stimulation such as viral infection. This mechanism may account for the loss of apparent tolerance to self antigens in autoimmune diseases such as insulin-dependent diabetes mellitus.

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