CD16+ human monocyte-derived dendritic cells matured with different and unrelated stimuli promote similar allogeneic Th2 responses: regulation by pro- and anti-inflammatory cytokines.
We previously demonstrated that tumor necrosis factor (TNF)-alpha-matured CD16- and CD16+ human monocyte-derived dendritic cells (16-mDC and 16+mDC) differentially stimulate naive CD4+ lymphocytes by inducing Th1- and Th2-like responses, respectively. Here, we further characterized the role of different DC maturation factors on Th polarization. Immature 16+mDC and 16-mDC (iDC) obtained by culture of purified monocytes with GM-CSF and IL-4 were maturated with (i) Toll-like receptor (TLR) ligands [lipopolysaccharide (LPS)], (ii) lymphocyte-derived (soluble CD40 ligand, IFN-gamma) and (iii) endogenous inflammatory stimuli [TNF-alpha, prostaglandin (PG)E2]. After activation with these stimuli, DC secrete IL-12 only in presence of LPS, and 16+mDC produced lower amounts of IL-12 and IL-10 than 16-mDC. Allogeneic CD4+CD45RO- lymphocytes co-cultured with 16+mDC secreted higher levels of IL-4 and IL-10 than those co-cultured with 16-mDC, regardless of the maturation stimuli. Results were similar when DC were activated with TLR-2 or TLR-3 ligands. The higher induction of IL-4 by 16+mDC was primarily dependent on IL-12, IL-4 and IL-10. IFN-gamma production by CD4+ T cells was similar with all the conditions except with LPS-16+mDC, which induced reduced amounts of this cytokine. Those differences were totally eliminated by neutralization of IL-12, IL-4 or IL-10. Finally, 16-mDC could reverse the Th2 phenotype of already committed lymphocytes toward a Th1 pattern in short-term cultures, whereas 16+mDC had less ability to skew this phenotype. These results indicate that 16+mDC elicit superior Th2 responses independently of the maturation factors that they received, and suggest that they could represent an important population of regulatory DC.
Rivas-Carvalho
Amaranta
A
Department of Molecular Biomedicine, Centro de Investigación y de Estudios Avanzados-IPN, Instituto de Investigaciones Biomédicas, UNAM, Mexico City, Mexico.
Meraz-Ríos
Marco A
MA
Santos-Argumedo
Leopoldo
L
Bajaña
Sandra
S
Soldevila
Gloria
G
Moreno-García
Miguel E
ME
Sánchez-Torres
Carmen
C
D016207:Cytokines / Q000502:physiology*; D003713:Dendritic Cells / Q000502:physiology*; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D009000:Monocytes / Q000166:cytology*; D017452:Receptors, IgG / Q000032:analysis*; D018418:Th2 Cells / Q000276:immunology*
D016207:Cytokines; D017452:Receptors, IgG; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma