Inhibition of heart allograft rejection with mitomycin C-treated donor dendritic cells.
We showed previously that dendritic cells (DCs) treated with mitomycin C (MMC) tolerize allogeneic T cells in vitro and this might be mediated by downregulation of CD80, CD86, and ICAM-1. Here we analyze the suppression of the T-cell response induced by MMC-DCs in vivo. Rats injected with allogeneic DCs developed a strong lymph node reaction, whereas MMC-DCs induced no reaction. The same effect was obtained when CD80, CD86, and ICAM-1 expressed by DCs were blocked with antibodies. One injection of donor MMC-DCs strongly prolonged heart allograft survival in a donor-specific manner. Suppression of rejection was also achieved when donor DCs were pretreated with a combination of anti-CD80, anti-CD86, and anti-ICAM-1 antibodies, showing that downregulation of these molecules confers the DCs inhibitory properties. We conclude that allogeneic MMC-DCs specifically inhibit the T-cell response in vivo and that downregulation of CD80, CD86, and ICAM-1 is a potential mechanism of this effect.
Jiga
Lucian P
LP
Institute of Immunology, Department of Transplantation Immunology, University of Heidelberg, Heidelberg, Germany. ljiga@umft.ro
Ehser
Sandra
S
Kleist
Christian
C
Opelz
Gerhard
G
Terness
Peter
P
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000637:transplantation; D015536:Down-Regulation; D006084:Graft Rejection / Q000517:prevention & control*; D016027:Heart Transplantation; D007165:Immunosuppression Therapy / Q000379:methods*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008213:Lymphocyte Activation; D016685:Mitomycin / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014019:Tissue Donors
D000906:Antibodies; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018799:Intercellular Adhesion Molecule-1; D016685:Mitomycin