Prevention of allograft rejection by in vitro generated tolerogenic dendritic cells.
Achieving immunological tolerance in transplantation has been a long sought-after goal since the 1960s. It is, therefore, interesting that the dendritic cells (DC), which are classically known as the most potent stimulators of T cell activation, are now also considered putative tools for tolerance induction. In line with this, much work has been performed using DC for vaccination and immune stimulation. Recently, great interest has been generated regarding the ability of DC to act as immune regulatory cells. Specific subsets of DC or immature DC (iDC) appear to be responsible for maintaining self-tolerance. In this review we will highlight our efforts at elucidating the contribution of DC in transplant tolerant in mice. Specifically, four strategies will be outlined that are currently being used for the generation of DC that have tolerogenic properties in the prevention of allograft rejection. The present study demonstrates that modulated iDC with blunted T cell stimulatory or antigen presentation abilities can afford transplant tolerance by minimizing T cell activation and proinflammatory cytokine production. Moreover, in an alternate strategy, normally matured DC have also been modulated such that alloreactive T cells are specifically targeted for deletion.
Ichim
Thomas E
TE
Department of Surgery, University of Western Ontario, London, Ont., Canada.
Zhong
Robert
R
Min
Wei-Ping
WP
D000818:Animals; D017951:Antigen Presentation; D003713:Dendritic Cells / Q000737:chemistry / Q000276:immunology / Q000637:transplantation*; D053222:Fas Ligand Protein; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D007108:Immune Tolerance; D018664:Interleukin-12 / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology; D016131:Lymphocyte Subsets / Q000276:immunology; D008285:Major Histocompatibility Complex; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D014162:Transfection; D023001:Transplantation Tolerance
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D018664:Interleukin-12