| Popis: |
After a short course of tacrolimus, Lewis rat liver allografts induce donor-specific nonreactivity in Brown Norway recipients that is immunosuppression independent after 28 days. To clarify the role of donor major histocompatibility complex (MIle) class II'" cells, we investigated the migration to the recipient splenic T- and B-cell compartments of different sub sets of Lewis MIle class II'" passenger leukocytes. The rise and decline of immune activation were monitored in the hepatic allograft and in the host spleen by anal yses of BrdU'" (proliferating) leukocytes, TUNEL + (ap optotic) cells, apoptosis-associated molecules, THlI TH2 cytokine profiles, and histoimmunocytochemical examination of graft and splenic tissues. Serial flow . cytometry studies during the 28-day period of drug assisted "hepatic tolerogenesis" showed that migra tory MIle class II+ cells accounted for less than half of the donor cells in the host spleen. The class II+ cells consisted mostly ofB cells that homed to splenic B-cell follicles with only a sp8J."Se representation of dendritic cells that were exclusively found in the splenic peri arteriolar lymphoid sheath. In parallel studies, trans plantation of the less tolerogenic heart produced a diminutive version of the same events, but with far fewer donor cells in the host spleen, evidence of sus tained immune activation, and the development of chronic rejection by 100 days. The data are consistent with the paradigm that migration of donor leukocytes is the prime determinant of variable tolerance induc tion induced by transplantation of the liver and other organs, but without regard for donor MIle class 11+ expression. |
