Functional plasticity of human respiratory tract dendritic cells:: GM-CSF enhances TH2 development

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-CSE. 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.