IL-10-generated tolerogenic dendritic cells are optimal for functional regulatory T cell induction--a comparative study of human clinical-applicable DC.
Tolerogenic dendritic cells (tDC) are a promising tool for specific cellular therapy to induce immunological tolerance in transplantation and autoimmunity. To date, most described tDC methods have not been converted into clinically applicable protocols and systematic comparison of required functional characteristics, i.e. migration and functional regulatory T cell (Treg) induction, is lacking. We compare clinical-grade tDC generated with vitamin D(3), IL-10, dexamethasone, TGFβ or rapamycin. For good migratory capacity and a stable phenotype, additional maturation of tDC was required. Maturation with a cocktail of TNFα, IL-1β and PGE(2) induced optimal migration. Importantly, all tDC showed a stable phenotype under pro-inflammatory conditions. Especially IL-10 DC showed most powerful tolerogenic characteristics with high IL-10 production and low T cell activation. Moreover, in a functional suppression assay only IL-10 DC induced Treg that strongly suppressed T cell reactivity. Thus, clinical-grade IL-10 DC show functional characteristics that make them best suited for tolerance-inducing therapies.
Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, University of Amsterdam, Academic Medical Center, Amsterdam, The Netherlands.
Martine A
MA
Boks
Judith R
JR
Kager-Groenland
Michiel S P
MS
Haasjes
Jaap Jan
JJ
Zwaginga
S Marieke
SM
van Ham
Anja
A
ten Brinke
D002465:Cell Movement; D002478:Cells, Cultured; D054421:Chemokine CCL21 / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology*; D010641:Phenotype; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000276:immunology
C515478:CCL21 protein, human; D054421:Chemokine CCL21; C508609:IL10 protein, human; D016212:Transforming Growth Factor beta; D016753:Interleukin-10