Generation of tolerogenic dendritic cells by treatment with mitomycin C: inhibition of allogeneic T-cell response is mediated by downregulation of ICAM-1, CD80, and CD86.
BACKGROUND
Deliberately generated tolerogenic dendritic cells (DC) might be a useful tool for induction of donor-specific tolerance in transplantation. In this article, the authors study the effect of mitomycin C (MMC)-treated DC on rat T cells and delineate the mechanism of their conversion into tolerogenic cells.


METHODS
The influence of MMC treatment on the capacity of DC to activate allogeneic T cells was tested in vitro, and the expression of cell surface molecules was studied by flow cytometry.


RESULTS
MMC-treated DC lose their allostimulatory capacity, and this cannot be attributed to cell death or release of MMC. Interestingly, suppressed T cells cannot be restimulated, indicating that MMC-treated DC induce tolerance. MMC treatment selectively decreases adhesion (intercellular adhesion molecule [ICAM]-1) and co-stimulatory (CD80, CD86) molecules. Functional blocking of these molecules with specific antibodies confers to DC the same T-cell-suppressive properties as treatment with MMC.


CONCLUSIONS
MMC treatment converts rat DC into tolerogenic cells. This mechanism is mediated by decrease of ICAM-1, CD80, and CD86.
Jiga
Lucian P
LP
Department of Transplantation Immunology, Heidelberg, Germany.
Bauer
Thomas M
TM
Chuang
Jing-Jing
JJ
Opelz
Gerhard
G
Terness
Peter
P
D000477:Alkylating Agents / Q000494:pharmacology*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D015536:Down-Regulation; D007108:Immune Tolerance; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D016685:Mitomycin / Q000494:pharmacology*; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology*; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000276:immunology*
D000477:Alkylating Agents; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497966:Cd86 protein, rat; D008562:Membrane Glycoproteins; D019384:Nucleic Acid Synthesis Inhibitors; D018799:Intercellular Adhesion Molecule-1; D016685:Mitomycin