A novel accelerated rejection model for mouse cardiac transplantation involving presensitization with donor splenocytes.
BACKGROUND
Accelerated rejection is a type of refractory rejection. Animal models of accelerated rejection are widely employed in research on transplant immunity.


METHODS
We divided 36 C57BL/6 mice into six groups that underwent heart transplant. To select the ideal number of splenocytes for the presensitization to induce accelerated rejection, were transferred 0.5 × 10(7), 1 × 10(7), 5 × 10(7), or 10 × 10(7) donor splenocytes 7 d before transplantation. We confirmed successful presensitization by increases in donor-reactive antibodies. We performed 12 additional heart transplants in the accelerated rejection group and the control groups for a histological examination, immunohistochemical staining for C3d, and a splenocyte test using flow cytometry.


RESULTS
The transfer of 5 × 10(7) donor splenocytes effectively and efficiently induced an accelerated rejection in the BALB/c→C57BL/6 heart transplant, with an allograft survival time that was decreased from 7.4 ± 0.5 d to 3.5 ± 0.8 d compared with the allogenic controls (P < 0.05, log-rank test). An analysis of this model indicated that compared with acute rejection, the number of donor-reactive antibodies was significantly increased, and the proportions of effector memory CD8(+) T cells and plasmacytes in the spleen were significantly increased (7.81% ± 1.2% versus 2.96% ± 1.0%, P = 0.006; 1.27% ± 0.13% versus 0.71% ± 0.22%, P = 0.018, respectively). We found the histological characteristics of both cellular and humoral rejection in the accelerated rejection model.


CONCLUSIONS
Presensitization via the transfer of donor splenocytes facilitates the establishment of an accelerated rejection model. Our findings with this model indicate that humoral rejection and cellular rejection are coexistent, and that the proportions of effector memory CD8(+) T cells and plasmacytes in the spleen increase significantly during accelerated rejection.
Department of Organ Transplantation, First Affiliated Hospital of Sun Yat-sen University, Guang Zhou, Guang Dong Province, China.
Gang
G
Zhang
Guodong
G
Chen
Longshan
L
Liu
Jiang
J
Qiu
Lizhong
L
Chen
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D006084:Graft Rejection; D016027:Heart Transplantation / Q000009:adverse effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology / Q000276:immunology*; D014019:Tissue Donors