| First Author | Seery JP | Year | 1999 |
| Journal | J Immunol | Volume | 162 |
| Issue | 12 | Pages | 7241-8 |
| PubMed ID | 10358171 | Mgi Jnum | J:55527 |
| Mgi Id | MGI:1338615 | Doi | 10.4049/jimmunol.162.12.7241 |
| Citation | Seery JP, et al. (1999) A central role for alpha beta T cells in the pathogenesis of murine lupus. J Immunol 162(12):7241-8 |
| abstractText | We have previously shown that female transgenic mice expressing IFN-gamma 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-gamma transgenic mice congenitally deficient in either alpha beta or gamma delta T cells. TCR delta-/- transgenics continued to produce antinuclear autoantibodies and to develop severe kidney lesions. In contrast, TCR beta-/- IFN-gamma transgenic mice failed to produce antinucleosome, anti-dsDNA, or antihistone autoantibodies, and kidney disease was abolished. Both alpha beta- and gamma delta-deficient transgenics continued to develop IFN-gamma-associated skin disease, lymphadenopathy, and splenomegaly. The data show that the autoantibody-mediated pathology of murine lupus in IFN-gamma transgenic mice is completely alpha beta T cell dependent and that gamma delta T cells cannot drive autoantibody production. These results imply that production of antinuclear autoantibodies in IFN-gamma 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. |
