The in-vitro inhibition of rat alloantigen presentation by immunotoxins--implications for allografting.
The removal of graft interstitial dendritic cells (IDC) prior to transplantation into a recipient has been shown to improve graft survival in a number of experimental studies. We report the in-vitro properties of two immunotoxins (IT) which could be used to deplete graft IDC when administered ex vivo by hypothermic perfusion in an experimental rat transplantation model. Ricin A chain (RAC) IT targeted at either class II major histocompatibility complex (MHC) molecules or leukocyte common antigens (LCA) were prepared. These IT had similar equilibrium constants, binding kinetics and inhibiting activity of cell-free protein synthesis. IT cytotoxicity was assessed by inhibition of alloantigen presentation by targeted low density spleen cells (LDSC) in a one way mixed lymphocyte culture (MLC). When LDSC were hypothermically incubated for 2 h with IT only the anti class II MHC IT inhibited the MLC and the maximum inhibition depended on the cell allotypes. The inhibition was increased to almost 100% when chloroquine was incorporated throughout the culture period.
Wiley
K N
KN
Urology Transplant Laboratories, Royal Hallamshire Hospital, Sheffield.
Clark
A
A
Fox
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D006084:Graft Rejection; D000922:Immunotoxins / Q000494:pharmacology*; D007519:Isoantigens / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D051381:Rats; D012276:Ricin / Q000494:pharmacology*; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D007519:Isoantigens; D012276:Ricin