TY - JOUR
T1 - The role of graft and host accommodation in a hamster-to-rat cardiac transplantation model
AU - Komori, Koji
AU - Fuchimoto, Yasushi
AU - Morikawa, Yasuhide
AU - Obara, Hideaki
AU - Kawachi, Shigeyuki
AU - Tanabe, Minoru
AU - Hoshino, Ken
AU - Shimazu, Motohide
AU - Matsuzaki, Yumi
AU - Kitajima, Masaki
PY - 2008/1
Y1 - 2008/1
N2 - 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.
AB - 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.
KW - Accommodation
KW - B-1 cell
KW - Protective gene
KW - Xenotransplantation
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U2 - 10.1097/01.tp.0000296030.88283.92
DO - 10.1097/01.tp.0000296030.88283.92
M3 - Article
C2 - 18192920
AN - SCOPUS:38149017014
SN - 0041-1337
VL - 85
SP - 112
EP - 117
JO - Transplantation
JF - Transplantation
IS - 1
ER -