The role of graft and host accommodation in a hamster-to-rat cardiac transplantation model.
BACKGROUND
We evaluated the importance and mechanism of graft and host accommodation in hamster-to-rat cardiac xenotransplantation models.


METHODS
To evaluate graft accommodation, accommodated hamster grafts (Group 2) were transplanted to naïve host rats treated with FK506, and compared with naïve hamster grafts (Group 1). To evaluate host accommodation, three groups were evaluated: naive hamster hearts were transplanted to naïve hosts treated with FK506 (Group 3: 0.5 mg/kg, Group 4: 1.0 mg/kg) and splenectomy, and compared with accommodating hosts (Group 5) with FK506 0.5 mg/kg and splenectomy. We examined graft survival, histopathology, antihamster antibodies and B-1 cells in blood.


RESULTS
Graft survival in Group 2 (3.4+/-0.9 days) was not significantly different from that in Group 1 (2.8+/-0.4 days). Graft survival in Groups 4 and 5 (>30 days) was significantly prolonged compared with that in Group 3 (6.0+/-0.7 days). Histopathology of Groups 1-3 showed humoral rejection, whereas Groups 4 and 5 showed normal histology and expression of protective genes. In Groups 1-3, antihamster immunoglobulin (Ig) M and B-1 cells increased significantly compared to Groups 4 and 5, where IgM and B-1 cells remained low or were reduced.


CONCLUSIONS
Host accommodation was more important than graft accommodation. Accommodating grafts expressing protective genes were rejected with an elevation of both IgM and B-1 cells. In accommodated hosts, both IgM and B-1 cells decreased, suggesting that B-1 cells may be responsible for the production of antihamster antibodies. These results suggest that sufficient suppression of B-1 cells, resulting in decreased titers of antihamster antibodies, may play an important role in host accommodation.
Komori
Koji
K
Department of Surgery, Keio University, School of Medicine, Tokyo, Japan.
Fuchimoto
Yasushi
Y
Morikawa
Yasuhide
Y
Obara
Hideaki
H
Kawachi
Shigeyuki
S
Tanabe
Minoru
M
Hoshino
Ken
K
Shimazu
Motohide
M
Matsuzaki
Yumi
Y
Kitajima
Masaki
M
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D018956:CD5 Antigens / Q000378:metabolism; D006224:Cricetinae; D006087:Graft vs Host Reaction / Q000187:drug effects / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology*; D006789:Host vs Graft Reaction / Q000187:drug effects / Q000276:immunology*; D007075:Immunoglobulin M / Q000097:blood; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008647:Mesocricetus / Q000276:immunology*; D023421:Models, Animal; D009206:Myocardium / Q000276:immunology / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew / Q000276:immunology*; D016559:Tacrolimus / Q000494:pharmacology; D014183:Transplantation, Heterologous / Q000276:immunology*
D018956:CD5 Antigens; D007075:Immunoglobulin M; D007166:Immunosuppressive Agents; D016559:Tacrolimus