CD4+ T Cell Responses Elicited by Different Subsets of Human Skin Migratory Dendritic Cells

Department of Dermatology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
The Journal of Immunology (Impact Factor: 4.92). 01/2006; 175(12):7905-15. DOI: 10.4049/jimmunol.175.12.7905
Source: PubMed


Skin dendritic cells (DC) are professional APC critical for initiation and control of adaptive immunity. In the present work we have analyzed the CD4+ T cell stimulatory function of different subsets of DC that migrate spontaneously from human skin explants, including CD1a+CD14- Langerhans' cells (LC), CD1a-CD14- dermal DC (DDC), and CD1a-CD14+ LC precursors. Skin migratory DC consisted of APC at different stages of maturation-activation that produced IL-10, TGF-beta1, IL-23p19, and IL-12p40, but did not release IL-12p70 even after exposure to DC1-driving stimuli. LC and DDC migrated as mature/activated APC able to stimulate allogeneic naive CD4+ T cells and to induce memory Th1 cells in the absence of IL-12p70. The potent CD4+ T cell stimulatory function of LC and DDC correlated with their high levels of expression of MHC class II, adhesion, and costimulatory molecules. The Th1-biasing function of LC and DDC depended on their ability to produce IL-23. By contrast, CD1a-CD14+ LC precursors migrated as immature-semimature APC and were weak stimulators of allogeneic naive CD4+ T cells. However, and opposite of a potential tolerogenic role of immature DC, the T cell allostimulatory and Th1-biasing function of CD14+ LC precursors increased significantly by augmenting their cell number, prolonging the time of interaction with responding T cells, or addition of recombinant human IL-23 in MLC. The data presented in this study provide insight into the function of the complex network of skin-resident DC that migrate out of the epidermis and dermis after cutaneous immunizations, pathogen infections, or allograft transplantation.

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    • "CD14+ migratory DDC are discernable from dermis-resident CD14+ dermal macrophages through their surface expression of CD1b and CD1c (24). In a comparative analysis with CD14− DDC, CD14+ DDC were shown to be poor inducers of allogeneic T cells and to require high DC:T cell ratios for Th1 induction (25). This relative inability of CD14+ DDC to induce Th1 cells was related to their release of IL-10 and TGFβ1. "
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    • "The functional consequence of CD1c þ DC capacity to produce both IL-23 and IL-12p70 is unclear but may imply plasticity for Th1 and Th17 response induction in different contexts . Isolated CD1c þ DCs are good stimulators of naı¨ve CD4 þ T cells but have inferior capacity to cross-present antigen to CD8 þ T cells in most reports (Bachem et al., 2010; Crozat, Guiton, Contreras, et al., 2010; Haniffa et al., 2009, 2012; Jongbloed et al., 2010; Morelli et al., 2005). Blood and lung CD1c þ DCs were superior to other DC subsets at inducing autologous Th17 polarization following DC stimulation with Aspergillus fumigatus (Schlitzer et al., 2013). "
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