Prolonged heart allograft survival resulted from donor-specific T-cell sequestering and removal by selective splenectomy in mice.
BACKGROUND
Selective splenectomy when donor antigen-specific activated T cells are sequestered in the recipient spleen may prolong allograft survival because of removal of all of these T cells.


OBJECTIVE
We investigated the effect on cardiac allograft survival in mice by means of removal of activated specific T cells by splenectomy.


METHODS
Donor (Balb/c) spleen cells were injected into primed allogeneic recipients (C57BL/6). Selective recipient splenectomy and donor-type cervical heart grafting in Balb/c to C57BL/6 from mice were examined at 0, 24, 48, and 72 hours after donor spleen cell infusion.


RESULTS
Control C57BL/6 mice rejected Balb/c heart grafts at 6.86 +/- 0.19 days. Delayed heart grafting plus splenectomy at 24 or 48 hours after donor-type spleen cell infusion significantly prolonged heart allograft survival (24 hours: 15.86 +/- 3.44 days, P < .001; 48 hours: 21.71 +/- 5.22 days, P < .001, respectively). However, 72-hour delayed heart grafting plus splenectomy failed to prevent acute rejection (72 hours: 9.57 +/- 2.51 days, P > .01). Immunohistochemistry showed, at 24 to 48 hours after donor antigen infusion, the recipient spleens characterized by an obvious increase in CD4+ CD8+ T cells in periateriolar lymphoid sheaths, marginal zones, and red pulp compared with the 72-hour group.


CONCLUSIONS
Transient accumulation of donor-specific activated T cells in the spleen of recipients provide an opportunity to remove all of these T cells by a surgical procedure. As the largest immune organ the spleen is the main place where T cells are activated and regenerated. At 24 or 48 hours when donor-specific T cells were sequestered in the spleen after donor antigen stimulation, selective recipient splenectomy was able to remove the T cells and prolong was allograft survival. Refinement of this protocol may eventually warrant clinical application.
Zhu
X H
XH
Institute of Organ Transplantation, Key laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
Chen
S
S
Chen
Z K
ZK
D000818:Animals; D006085:Graft Survival / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology*; D008212:Lymphocyte Depletion / Q000379:methods*; D017710:Lymphocyte Transfusion; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000276:immunology; D013156:Splenectomy; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors; D014184:Transplantation, Homologous / Q000276:immunology