Prolongation of lung xenograft survival in rats with a short course of deoxyspergualin and cyclosporin A.
The efficacy of 15-deoxyspergualin (DSG), cyclosporin A (CyA), and splenectomy--alone or in combination--in prolonging the survival of concordant lung xenotransplants was studied in the hamster-to-rat model. In the untreated group, rejection occurred within 3 days, with an elevation of lymphocytotoxic antibody titers. The rejected lung revealed that ED1 + cells were more prevalent than MRC OX8 + cells in the perivascular infiltrates. In the DSG group, the antibody response was suppressed and median survival increased to 7.5 days. The rejected lungs demonstrated a highly significant depression in ED1 + cellular infiltration and a moderate MRC OX8 + cellular infiltration. When maintenance CyA was combined with a short course of DSG, survival dramatically increased to beyond 100 days. There were no deposits of IgM, IgG, or C3 or of any cell infiltrate in the grafts of two animals sacrificed 107 and 119 days post-transplantation. We conclude that initial treatment with DSG combined with continuous CyA can suppress acute rejection in the hamster-to-rat lung xenograft model, resulting in long-term graft survival.
Nagayasu
T
T
First Department of Surgery, Nagasaki University School of Medicine, Japan.
Kawahara
K
K
Takahashi
T
T
Ide
S
S
Sasaki
N
N
Shingu
H
H
Yamamoto
S
S
Yamasaki
N
N
Ayabe
H
H
D000818:Animals; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D006224:Cricetinae; D016572:Cyclosporine / Q000627:therapeutic use*; D003602:Cytotoxicity, Immunologic; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology; D006085:Graft Survival / Q000187:drug effects*; D006146:Guanidines / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016040:Lung Transplantation / Q000276:immunology* / Q000473:pathology / Q000502:physiology; D016131:Lymphocyte Subsets / Q000276:immunology; D008297:Male; D008647:Mesocricetus; D009206:Myocardium / Q000473:pathology; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D013156:Splenectomy; D013997:Time Factors; D014183:Transplantation, Heterologous / Q000276:immunology* / Q000473:pathology / Q000502:physiology
D015704:CD4 Antigens; D016827:CD8 Antigens; D006146:Guanidines; D007166:Immunosuppressive Agents; D016572:Cyclosporine; C037258:gusperimus