A central role for alpha/beta T cells in the pathogenesis of murine lupus

We have previously shown that female transgenic mice expressing IFN-gamma i n the epidermis, under the control of the involucrin promoter, develop infl ammatory skin disease and a form of murine lupus, To investigate the pathog enesis of this syndrome, we generated female IFN-gamma transgenic mice cong enitally deficient in either alpha beta or gamma delta T cells. TCR delta(- /-) transgenics continued to produce antinuclear autoantibodies and to deve lop severe kidney lesions. In contrast, TCR beta(-/-) IFN-gamma transgenic mice failed to produce antinucleosome, anti-dsDNA, or antihistone autoantib odies, and kidney disease was abolished. Both alpha beta- and gamma delta-d eficient transgenics continued to develop IFN-gamma-associated skin disease , lymphadenopathy, and splenomegaly. The data show that the autoantibody-me diated pathology of murine lupus in IFN-gamma transgenic mice is completely cup T cell dependent and that gamma delta T cells cannot drive autoantibod y production. These results imply that production of antinuclear autoantibo dies in IFN-gamma transgenic animals is Ag driven, and we identified cluste rs 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 t o the human disease.