학술논문

Functional Compartmentalization Following Induction of Long-Term Graft Survival with Pregraft Donor-Specific Transfusion
Document Type
Article
Source
American Journal of Transplantation; March 2007, Vol. 7 Issue: 3 p538-549, 12p
Subject
Language
ISSN
16006135; 16006143
Abstract
Long-term survival is achieved in rat recipients by pre-graft donor-specific blood transfusion. We characterized the immune compartments in long-term survivors and analyzed them for capacity to transfer tolerance and protect against chronic rejection. Splenocytes and spleen T cells from treated recipients transferred long-term graft survival to 100 of secondary recipients. In contrast, blood transferred graft survival to only 50 of recipients whereas blood T cells had no effect. An unaltered TCR repertoire, an increase in suppressive CD4CD25T cells, a decrease in antidonor T-cell proliferative response and normal perforin-granzyme levels were the hallmarks of the spleen T cells. Blood T cells were characterized by a strongly altered CD8repertoire, normal CD4CD25T cell number with unchanged antidonor T-cell proliferative response, an activated T-cell phenotype and an increase in perforin-granzyme levels. However, following the transfer of blood or spleen cells into secondary recipients, all grafts displayed chronic rejection. These findings provide evidence that distinct compartments play critical roles in DST recipients. Regulatory cells do not accumulate in blood, which appears to be a reservoir for cytotoxic T cells. Spleen T cells, which display a regulatory-like profile and transfer graft survival, are not able to prevent chronic rejection.