CD40 engagement strongly induces CD25 expression on porcine dendritic cells and polarizes the T cell immune response toward Th1.
Orientation of the immune response toward Th1, Th2, Th17 or Treg plays an important role in self-tolerance and defence against pathogens and tumors. However, this orientation has not been fully characterised in the pig and little is known about the influence of maturation stimulus on the capacity of dendritic cells selectively to direct different types of Th cell responses. Dendritic cell (DC) maturation can be induced by different agents such as inflammatory cytokines, TLR ligands and CD40L. However, the role of the latter in the maturation of pig DC has never been reported. In this study we analysed how different maturation agents influence the capacity of DC to skew the immune response. Monocyte-derived porcine DCs were matured with human CD40L-transfected L-cells, Lipopolysaccharide (LPS) alone or LPS in combination with Tumor necrosis factor-alpha (TNFalpha) and interferon-alpha (IFNalpha). We found that human CD40L induced DC maturation characterised by increased expression of co-stimulatory CD80/86 molecules, high production of IL-12p40 in DC and induction of IFNgamma and t-bet mRNA in T cells, suggesting a Th1 orientation. Moreover we report for the first time the appearance of CD25 after activation of porcine DC. Furthermore, DC activated with TNF+LPS+IFN showed the highest allo-stimulatory capacity of allogeneic lymphocytes and induced IL-17 mRNA in T lymphocytes, suggesting a Th17 orientation that has never been previously reported in the pig. We also showed that immature DCs did not produce any IL-10 or IL-12 and induced both GATA-3 and IL-13 transcription in allogeneic MLR suggesting a Th2 orientation. This study therefore underlines that the nature of the stimulus strongly influences the capacity of DC to steer the immune response in the pig.
Pilon
Caroline
C
Université François Rabelais, EA 4245 Cellules Dendritiques, Immunomodulation et Greffes, IFR 136, UFR de Médecine, Tours, France.
Levast
Benoit
B
Meurens
François
F
Le Vern
Yves
Y
Kerboeuf
Dominique
D
Salmon
Henry
H
Velge-Roussel
Florence
F
Lebranchu
Yvon
Y
Baron
Christophe
C
D000818:Animals; D019013:CD40 Antigens / Q000276:immunology*; D023201:CD40 Ligand; D002454:Cell Differentiation / Q000187:drug effects; D048430:Cell Shape; D045142:Cross-Priming / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000648:ultrastructure; D006801:Humans; D007372:Interferons / Q000494:pharmacology; D016753:Interleukin-10 / Q000096:biosynthesis; D053762:Interleukin-12 Subunit p40 / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D010641:Phenotype; D034421:Sus scrofa; D018417:Th1 Cells / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D019013:CD40 Antigens; D016207:Cytokines; D053762:Interleukin-12 Subunit p40; D053645:Interleukin-2 Receptor alpha Subunit; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D023201:CD40 Ligand; D007372:Interferons