Dendritic cells activated by lipopolysaccharide after dexamethasone treatment induce donor-specific allograft hyporesponsiveness.
BACKGROUND
Immature dendritic cells (imDC) can prolong allograft survival in murine transplantation models. Recent data indicate that semi-mature or alternatively activated DC (aaDC) may be even more tolerogenic.


METHODS
We compared the phenotype and regulatory capacity of: a) imDC, cultured in the presence of dexamethasone (DEX), b) mature DC (matDC), activated with LPS, and c) aaDC, activated with LPS after pretreatment with DEX.


RESULTS
As compared to imDC, aaDCs displayed a slight upregulation of CD40 while expression levels of MHC-II and CD86 remained low. The production of proinflammatory cytokines, in particular IL-12, by aaDC was much lower than by matDC while both produced similar amounts of the regulatory cytokine IL-10 leading to an increased IL-10/IL-12 ratio for aaDC. After infusion of donor type aaDCs, responder cells isolated from the recipient mice showed donor-specific hyporesponsiveness to restimulation by matDC. Infusion of matDC was immunogenic, while imDC induced partial hyporesponsiveness. Importantly, pretreatment with donor type aaDC (but not imDC) resulted in prolonged survival of a completely MHC-mismatched heart allograft.


CONCLUSIONS
Alternatively activated DC are more efficacious than the classical imDC in the regulation of the alloimmune response, which may be related to a distinct cytokine profile characterized by an increased IL-10/IL12 ratio.
Emmer
Peter M
PM
Department of Nephrology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, the Netherlands.
van der Vlag
Johan
J
Adema
Gosse J
GJ
Hilbrands
Luuk B
LB
D000818:Animals; D000941:Antigens; D001854:Bone Marrow Cells / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D003907:Dexamethasone / Q000494:pharmacology*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006085:Graft Survival / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology; D007156:Immunologic Memory; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008198:Lymph Nodes / Q000378:metabolism; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D013154:Spleen / Q000378:metabolism; D023001:Transplantation Tolerance / Q000276:immunology*
D000941:Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D008070:Lipopolysaccharides; D003907:Dexamethasone