Graft-versus-host disease in severe combined immunodeficiency/beige mice administered canine leukocytes

This report describes the development and lesions of graft-versus-host disease (GVHD) in severe combined immunodeficiency/ beige (SCID/BG) mice after the administration of canine leukocytes. Intraperitoneal injections of 0.87 x 10(7) canine lymphocytes were given to each of 9 mice; 5 mice received no canine lymphocytes. Morphologic evidence of successful engraftment included peritoneal aggregates of lymphocytes and repopulation of spleen and lymph nodes by lymphocytes. Canine CD45R was expressed by 2.25% of peripheral blood leukocytes in the 1 mouse tested 65 d after engraftment but by none of the cells of a control mouse. Canine immunoglobulin G was detected in serum samples from 5 of the 6 tested mice given canine lymphocytes but none of the control mice. By 13 to 65 d after receiving canine lymphocytes, 5 of the 9 mice had died of GVHD or had been euthanized because of it; all the control mice remained healthy. Lesions of GVHD included hemolytic anemia, cholangiohepatitis, alveolitis, and disseminated intravascular coagulation. Serum from the donor dog and from all 15 randomly selected dogs caused agglutination of normal mouse erythrocytes, supporting a diagnosis of immune-mediated hemolytic anemia in the dog-mouse chimeras. All of the mouse serum tested contained murine immunoglobulin, and this "leakiness" may have contributed to the development of GVHD.