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Neonatal dendritic cells are intrinsically biased against Th-1 immune responses - PubMed

Comparative Study

Neonatal dendritic cells are intrinsically biased against Th-1 immune responses

C L Langrish et al. Clin Exp Immunol. 2002 Apr.

Abstract

Dendritic cells (DCs) were derived from human peripheral blood monocytes or cord blood monocytes cultured in the presence of IL-4 and GM-CSF. Adult and cord DCs were observed to have comparable immature phenotypes. However, the increase in surface expression of HLA-DR and CD86 after addition of LPS was significantly attenuated in cord DCs, with CD25 and CD83 expression also markedly reduced. Cord DCs were also unable to produce IL-12p70, failed to down-regulate expression of the chemokine receptor CCR5 and induced lower levels of IFN-gamma production from allogeneic naive CD4+ T cells than their adult counterparts. In contrast, the kinetics of the production of TNF-alpha and IL-10 in response to LPS stimulation was comparable to adult DCs. The reduced ability of cord DCs to attain a fully mature adult phenotype, and to activate naive CD4+ T cells to produce IFN-gamma, suggests that they are intrinsically preprogrammed against the generation of Th-1 immune responses.

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Figures

Fig. 1
Fig. 1

Phenotypic analysis of adult and cord response to LPS. Immature adult and cord DCs showed comparable surface marker expression (a, filled plots). Shifts in marker expression of DCs stimulated with 0·5 μg/ml LPS for 24h were overlayed (a, open plots). Adult DCs dramatically up-regulated HLA-DR (b) and CD86 (c) marker expression MFI; cord DCs, however, had little or no response. The values represent the means of 10 independent experiments, *P =0· 04 and **P =0·007. ■, Immature; formula image00017;, 24-h LPS.

Fig. 2
Fig. 2

Cytokine profiles of cord and adult DCs stimulated with LPS. The production of cytokines by adult and cord DCs was measured by ELISA, after different durations of LPS stimulation. Representative kinetic profiles from five independent experiments of IL-12p70 (a), IL-10 (b) and TNF-α (c) are shown. □, Cord; ■ adult.

Fig. 3
Fig. 3

DC stimulation of allogeneic naïve CD4+ T cells to produce IFN-γ. Adult and cord DCs stimulation of naive CD4+CD45RO– cells to produce IFN-γ, using either immature DCs (filled bars) or DCs activated with 0·5 μg/ml LPS for 8h (dotted bars) or 24h (striped bars). IFN-γ production was measured by intracellular cytokine staining (a) and ELISpot (b). For ELISpot, the number of spot-forming cells (SFC) per 1 × 106 cells was determined. The values represent the means of three independent experiments ± 1s.e.m. ■, Immature; formula image00004;, 8-h LPS; formula image00017;, 24-h LPS.

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References

    1. Kovarik J, Siegrist CA. Immunity in early life. Immunol Today. 1998;19:150–2. - PubMed
    1. Adkins B. T-cell function in newborn mice and humans. Immunol Today. 1999;220:330–5. - PubMed
    1. Harris DT, Schumacher MJ, Locascio J, et al. Phenotypic and functional immaturity of human umbilical cord blood T lymphocytes. Proc Natl Acad Sci USA. 1992;89:10006–10. - PMC - PubMed
    1. Wilson CB, Lewis DB. Basis and implications of selectively diminished cytokine production in neonatal susceptibility to infection. Rev Infec Dis. 1990;12:S410–S420. - PubMed
    1. Steinman RM. The dendritic cell and its role in immunogenicity. Ann Rev Immunol. 1991;8:271–96. - PubMed

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