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ß T Cells in the Pathogenesis of Murine Lupus1
*
Keratinocyte Laboratory and
Lymphocyte Molecular Biology Laboratory, Imperial Cancer Research Fund, London, United Kingdom; and
Department of Histopathology, St Mary’s Hospital Medical School, Imperial College of Science, Technology and Medicine, London, United Kingdom
We have previously shown that female transgenic mice expressing
IFN-
in the epidermis, under the control of the involucrin promoter,
develop inflammatory skin disease and a form of murine lupus. To
investigate the pathogenesis of this syndrome, we generated female
IFN- transgenic mice congenitally deficient in either 
ß or
T cells. TCR-/- transgenics continued to
produce antinuclear autoantibodies and to develop severe kidney
lesions. In contrast, TCRß-/- IFN- transgenic mice
failed to produce antinucleosome, anti-dsDNA, or antihistone
autoantibodies, and kidney disease was abolished. Both ß- and
-deficient transgenics continued to develop IFN--associated
skin disease, lymphadenopathy, and splenomegaly. The data show that the
autoantibody-mediated pathology of murine lupus in IFN- transgenic
mice is completely ß T cell dependent and that T cells
cannot drive autoantibody production. These results imply that
production of antinuclear autoantibodies in IFN- transgenic animals
is Ag driven, and we identified clusters of apoptotic cells in the
epidermis of the mice as a possible source of self Ags. Our findings
emphasize the relevance of this murine lupus model to the human
disease.
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