Induction of a syngeneic graft-versus-host disease-like syndrome in DBA/2 mice.
Syngeneic graft-versus-host disease has been shown to occur in syngeneic rat radiation chimeras after treatment with a short course of CsA. However, data concerning this model have been controversial in murine systems. We have successfully induced a GVHD-like syndrome in syngeneic mouse radiation chimeras treated transiently with CsA. Lethally irradiated (950 rads) DBA/2 mice were reconstituted with syngeneic bone marrow and treated daily, i.p. with 15 mg/kg CsA in olive oil for 21 days. Within 1 week after discontinuing CsA, animals developed clinical signs of GVHD including runting, hunched posture, and severe diarrhea. This disease was fatal for greater than 80% of treated animals within 4 weeks after cessation of CsA. Furthermore, the induction of syngeneic GVHD did not appear to be linked to a particular MHC haplotype. Histologically, there was pronounced lymphoid atrophy of the spleen and thymus. Sections of large intestine showed an acute inflammatory process involving the mucosal layer ranging from single-cell destruction to complete mucosal ulceration. This murine model of GVHD should provide new opportunities for studying the development and regulation of autoimmune processes.
Bryson
J S
JS
Department of Microbiology/Immunology, College of Medicine, University of Kentucky, Lexington 40536-0084.
Jennings
C D
CD
Caywood
B E
BE
Kaplan
A M
AM
D000818:Animals; D016026:Bone Marrow Transplantation; D003524:Cyclosporins / Q000633:toxicity*; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology* / Q000473:pathology; D008285:Major Histocompatibility Complex; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D013601:T-Lymphocytes / Q000276:immunology; D014185:Transplantation, Isogeneic
D003524:Cyclosporins