SENSITIZATION TO SELF (VIRUS) ANTIGEN BY IN-SITU EXPRESSION OF MURINE INTERFERON-GAMMA

被引:54
作者
LEE, MS
VONHERRATH, M
REISER, H
OLDSTONE, MBA
SARVETNICK, N
机构
[1] Scripps Res Inst, DEPT NEUROPHARMACOL, LA JOLLA, CA 92037 USA
[2] HARVARD UNIV, SCH MED, DEPT PATHOL, BOSTON, MA 02115 USA
关键词
AUTOIMMUNITY; TRANSGENIC MICE; PANCREATIC ISLETS; DIABETES; B7-1;
D O I
10.1172/JCI117689
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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 lFN-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 lFN-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.
引用
收藏
页码:486 / 492
页数:7
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