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1.
J Allergy Clin Immunol ; 116(5): 1136-43, 2005 Nov.
Article in English | MEDLINE | ID: mdl-16275388

ABSTRACT

BACKGROUND: Dendritic cells within the human respiratory mucosa (RTDCs) are proposed to initiate immune responses to foreign antigens. Their capacity to polarize T-cell responses, however, has not been investigated. OBJECTIVE: To compare RTDCs with peripheral blood dendritic cells (PBDCs) with regard to phenotype, cytokine production, capacity to polarize T-cell responses, and effects of exposure to the pleiotropic cytokine, GM-CSF. METHODS: CD1a(+) RTDCs and CD1c(+) PBDCs were purified from nasal turbinates of patients with nonatopic rhinitis and peripheral blood of healthy individuals, respectively. In some experiments, matched CD1c(+) RTDCs and PBDCs from patients with rhinitis were compared. The phenotype of DC was examined by flow cytometry and cytokine production by cytometric bead array. DCs were cocultured with allogeneic naive CD4(+) T cells, and cytokine production was determined by immunophenotyping, cytometric bead array, and ELISA. RESULTS: Both RTDCs and PBDCs exhibited an immature phenotype, but RTDCs expressed lower levels of MHC class II antigen. Cross-linking of CD40 on PBDCs, but not RTDCs, induced production of IL-12p70. In mixed lymphocyte cultures, RTDCs induced a T(H)1/T(H)2 profile, whereas PBDCs induced a T(H)1 profile. Exposure of RTDCs to GM-CSF induced a T(H)2 pattern of response in the mixed lymphocyte cultures. In contrast, exposure of PBDCs to GM-CSF promoted a T(H)1 response. CONCLUSION: This report emphasizes the importance of studying tissue-derived primary DCs, demonstrates functional plasticity of RTDCs, and implicates GM-CSF in amplifying the potential of RTDCs to initiate T(H)2 responses in the airways.


Subject(s)
Dendritic Cells/immunology , Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology , Respiratory Mucosa/cytology , Respiratory Mucosa/immunology , Th2 Cells/cytology , Adult , Antigens, CD1/metabolism , Blood Cells/cytology , CD4-Positive T-Lymphocytes/metabolism , Cell Differentiation/drug effects , Cells, Cultured , Coculture Techniques , Cytokines/biosynthesis , Dendritic Cells/cytology , Dendritic Cells/metabolism , Glycoproteins/metabolism , Humans , Middle Aged , Myeloid Cells/physiology , Phenotype
2.
Immunology ; 105(2): 155-62, 2002 Feb.
Article in English | MEDLINE | ID: mdl-11872090

ABSTRACT

Chemokines and their receptors regulate cell migration to sites of inflammation. The glucocorticoid dexamethasone has potent anti-inflammatory effects, yet paradoxically up-regulates expression of some cytokine receptors. We have examined the effects of dexamethasone on chemokine receptor expression. Using an RNase protection assay, we show that dexamethasone up-regulates human peripheral blood mononuclear cell (PBMC) expression of CXCR4 mRNA. Flow cytometric analysis demonstrated that increased expression of CXCR4, but not CXCR1 and CXCR2, occurred on both monocytes and CD3+ T cells in PBMC mixed cultures. A stromal-derived factor (SDF)-1alpha-mediated calcium influx was detected on monocytes. Basal levels of CXCR4 expression on purified monocytes were lower when compared with monocytes in mixed PBMC cultures. Co-culture of monocytes with purified CD3+ T cells led to enhanced basal expression of CXCR4 on monocytes. The use of transwells to partition CD3+ T cells resulted in increased CXCR4 expression on monocytes, suggesting that CD3+ T-cell derived soluble factors regulate CXCR4 expression.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Dexamethasone/pharmacology , Glucocorticoids/pharmacology , Monocytes/drug effects , Receptors, CXCR4/drug effects , Up-Regulation/drug effects , Biological Factors/physiology , CD3 Complex/analysis , Cells, Cultured , Chemokine CXCL12 , Chemokines, CXC/physiology , Coculture Techniques , Humans , Monocytes/immunology , Monocytes/metabolism , RNA, Messenger/genetics , Receptors, CXCR4/blood , Receptors, CXCR4/genetics , Solubility , T-Lymphocyte Subsets/metabolism
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