| Popis: |
Background. Normally, a Buffalo (BUF) recipient (RT1 b ) rejects a heterotopically transplanted Lewis (LEW) heart (RT1 1 ) drained into the portal vein (PV) within 14 days. However, the addition of PV administration of 25x10 6 ultraviolet B (UVB)-treated LEW spleen cells (SC) to BUF recipients 7 days before cardiac transplantation results in 70% long-term allograft survival. Methods. In this study, we used gadolinium chloride (GdC1 3 ) (7 mg/kg/day) to selectively block the phagocytosis of recipient hepatic Kupffer cells before PV injection of UVB-treated donor SC to examine the mechanism of tolerance induction, as measured by in vitro analysis of mixed lymphocyte culture (MLC), T cell cytotoxicity, T helper cell precursors (pTH), and cytotoxic T cell precursors (pCTL) by limiting dilution analysis. Results. A BUF recipient that received untreated or γ-irradiated LEW SC intraportally reacted to in vitro stimulation by LEW alloantigen with increased MLC proliferation, T cell cytotoxicity, pTH and pCTL frequencies, and interleukin-2 production. In contrast, SC from BUF that received UVB-treated LEW SC were hyporesponsive on MLC stimulation by donor LEW alloantigen and exhibited markedly reduced cytotoxicity, pTH and pCTL frequency, and interleukin-2 production. However, normal in vitro responsiveness resulted with stimulation by third-party Brown-Norway (RTI n ) SC, thus indicating that the systemic hyporesponsiveness was specific for the UVB donor alloantigen given PV. On the other hand, GdCl 3 given by intravenous injection daily for 3 days before PV alloantigen blocked the induction of in vitro hyporesponsiveness. Conclusion. Therefore, prevention of alloantigen sequestration by GdCl 3 inhibition of hepatic Kupffer cell phagocytosis was pivotal in preventing the development of portal venous tolerance. |
