Mechanisms of allergy and clinical immunologyHuman immature myeloid dendritic cells trigger a TH2-polarizing program via Jagged-1/Notch interaction
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Donors
Human PBMCs used in this study were obtained in accordance with the ethical standards of the responsible regional committee on human experimentation.
For reagents and antibodies, flow cytometry analysis, isolation of CD4+, CD14+, CD45RA+, CD45RO+ and BDCA-1+ cell, generation of DCs and of short term T-cell cultures, RNA isolation, cDNA synthesis and real-time quantitative RT-PCR, evaluation of TCR Vβ repertoire by spectratyping, Western blot analysis, siRNA delivery, and gene silencing, refer to
Culturing CD4+ T cells with myeloid iDCs results in the development of TH2-polarized cells
To understand the role of myeloid DCs on the process of TH1/TH2 polarization, we compared the cytokine production profile of CD4+ T-cells present in streptokinase-stimulated or Dermatophagoides pteronyssinus group 1 (Der p 1)–stimulated PBMCs of healthy nonatopic donors with that of CD4+ T cells stimulated with the same antigens in presence of autologous DCs obtained in vitro by culturing CD14+ cells with IL-4 plus GM-CSF. As shown in previous studies,16 after stimulation of whole PBMCs with
Discussion
Dendritic cells are a complex and heterogeneous family of cells that play an important role in the innate as well as the subsequent adaptive immune responses because they are capable of antigen uptake, processing, and presentation to T cells.20 At least 2 distinct pathways of DC development have been identified in mice, myeloid and lymphoid,21, 22 which differ in phenotype, localization, and function.21 In human beings, DCs represent 1% to 2% of PBMCs and are made up of at least 2 major subsets
References (34)
Human TH1 and TH2 cells: doubt no more
Immunol Today
(1991)- et al.
Expanding the effector CD4 T-cell repertoire: the TH17 lineage
Curr Opin Immunol
(2006) - et al.
Transcriptional regulation of TH1/TH2 polarization
Immunol Today
(2000) - et al.
STAT-6-independent GATA-3 autoactivation directs IL-4-independent TH2 development and commitment
Immunity
(2000) - et al.
Instruction of distinct CD4 T helper cell fates by different notch ligands on antigen-presenting cells
Cell
(2004) - et al.
Regulation of αβ/γδ T cell lineage commitment and peripheral T cell responses by Notch/RBP-J signaling
Immunity
(2004) - et al.
Notch directly regulates Gata3 expression during T helper 2 cell differentiation
Immunity
(2007) - et al.
CXCR3-mediated opposite effects of CXCL10 and CXCL4 on TH1 or TH2 cytokine production
J Allergy Clin Immunol
(2005) - et al.
Redirection of allergen-specific TH2 responses by a modified adenine through Toll-like receptor 7 interaction and IL-12/IFN release
J Allergy Clin Immunol
(2006) Regulation of the development of type 2 T-helper cells in allergy
Curr Opin Immunol
(1994)
Exposure to farming in early life and development of asthma and allergy: a cross-sectional survey
Lancet
Immunologic influences on allergy and the TH1/TH2 balance
J Allergy Clin Immunol
Acinetobacter lwoffi and Lactococcus lactis strains isolated from farm cowsheds possess strong allergy-protective properties
J Allergy Clin Immunol
Coming back to a missing immune deviation as main explanatory mechanism for the hygiene hypothesis
J Allergy Clin Immunol
Reversal of human allergen-specific CRTH2+ TH2 cells by IL-12 or the PS-DSP30 oligodeoxynucleotide
J Allergy Clin Immunol
TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties
Annu Rev Immunol
Lymphokine production by human T cells in disease states
Annu Rev Immunol
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Supported by the Italian Ministry of Education (40%), the Italian Ministry of Health grant by Ente Cassa di Risparmio, Florence, Italy (AIDS Project), EU Projects SENS-IT-IV (FP6-LSBH-CT-2006-018861), INNOCHEM (FP6-LSHB-CT-2005-518167), Agenzia Spaziale Italiana MoMa (WP ref: 1B1241-X5), and the German Federal Ministry of Education and Research (BMBF): 0313066F, 0313068C01 and 01 GS 0413 (NGFN-2: SIPAGE).
Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest.
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These authors contributed equally to this work.