Mechanisms of drug-induced lupus .3 Sex-specific differences in T cell homing may explain increased disease severity in female mice

Objective. To determine if sex-specific differences in lymphocyte trafficking could contribute to increased disease severity in female mice. Methods. A lupus-like disease was induced by injecting male and female mice with procainamide-treated T cell clones. Trafficking was examined by labeling the injected cells with Cr-51 or 5-chloromethylfluorescein diacetate. Results. Females developed more autoimmune liver disease and greater titers of anti-DNA antibodies than did males, and 2-7 times more cells accumulated in the female spleens. Splenectomy prevented the development of autoantibodies and renal and liver disease. Oophorectomy decreased the splenic homing, autoantibody titer, and liver disease severity, to levels found in males. Conclusion. T cells traffic differently to the spleen in male and female mice, and the spleen appears to be essential in the disease process. This suggests that differences in T cell homing could contribute to sex-specific disease severity in this murine model, and also possibly in human disease.