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

M. S. Lee, M. Von Herrath, H. Reiser, M. B.A. Oldstone, N. Sarvetnick

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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-γ could stimulate these cells to cytotoxic competency. For this purpose, we produced double transgenic mice expressing pancreatic IFN-γ as well as lymphocytic choriomeningitis virus (LCMV) nucleoprotein (NP) or glycoprotein (GP) antigen. 100% of the NP+/IFN-γ+ mice became diabetic before 2 mo of age, while none of the NP single transgenic littermates and only 10% of IFN-γ single transgenic littermates did. Strikingly, NP+/IFN-γ+ mice spontaneously developed cytotoxic T lymphocyte activity on LCMV-infected targets and vaccinia virus-NP-infected ones without prior LCMV infection but NP+/IFN-γ- mice did not, which indicates specific sensitization to the viral antigen by IFN-γ. These results suggest that lymphocytes ignorant of self antigens can be activated by IFN-γ 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.

Original languageEnglish (US)
Pages (from-to)486-492
Number of pages7
JournalJournal of Clinical Investigation
Volume95
Issue number2
StatePublished - Jan 1 1995

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Nucleoproteins
Autoantigens
Interferons
Viruses
Lymphocytic choriomeningitis virus
Viral Antigens
Virus Diseases
Autoimmune Diseases
Lymphocytes
Choristoma
Vaccinia virus
Cytotoxic T-Lymphocytes
Type 1 Diabetes Mellitus
Transgenic Mice
Immunization
Glycoproteins
T-Lymphocytes
Antigens

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Sensitization to self (virus) antigen by in situ expression of murine interferon-γ. / Lee, M. S.; Von Herrath, M.; Reiser, H.; Oldstone, M. B.A.; Sarvetnick, N.

In: Journal of Clinical Investigation, Vol. 95, No. 2, 01.01.1995, p. 486-492.

Research output: Contribution to journalArticle

Lee, MS, Von Herrath, M, Reiser, H, Oldstone, MBA & Sarvetnick, N 1995, 'Sensitization to self (virus) antigen by in situ expression of murine interferon-γ', Journal of Clinical Investigation, vol. 95, no. 2, pp. 486-492.
Lee, M. S. ; Von Herrath, M. ; Reiser, H. ; Oldstone, M. B.A. ; Sarvetnick, N. / Sensitization to self (virus) antigen by in situ expression of murine interferon-γ. In: Journal of Clinical Investigation. 1995 ; Vol. 95, No. 2. pp. 486-492.
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