Prolonged heart allograft survival resulted from donor-specific T-cell sequestering and removal by selective splenectomy in mice

Abstract

Introduction 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. Objectives 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 exammed 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 eventully warrant clinical application.