International Immunology Advance Access originally published online on July 26, 2004
International Immunology 2004 16(9):1251-1263; doi:10.1093/intimm/dxh127
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© 2004 The Japanese Society for Immunology
CD16+ human monocyte-derived dendritic cells matured with different and unrelated stimuli promote similar allogeneic Th2 responses: regulation by pro- and anti-inflammatory cytokines
1 Department of Molecular Biomedicine and 2 Department of Cellular Biology, Centro de Investigación y de Estudios Avanzados-IPN, 3 Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del IPN and 4 Department of Immunology, Instituto de Investigaciones Biomédicas, UNAM, Mexico City, Mexico
Correspondence to: C. Sánchez-Torres; E-mail: csanchez{at}mail.cinvestav.mx
We previously demonstrated that tumor necrosis factor (TNF)-
-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-
) and (iii) endogenous inflammatory stimuli [TNF-, 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- 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.
Keywords: allogeneic CD4+ T cell differentiation, antigen presenting cell subsets
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