Article

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: 5.36). 01/2006; 175(12):7905-15. DOI: 10.4049/jimmunol.175.12.7905
Source: PubMed

ABSTRACT 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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    • "The few studies analyzing the comparative phenotypic and functional properties of human epidermal and dermal DCs are much debated, probably owing to the methods of cell recovery, purification, or identification (Morelli et al., 2005; Klechevsky et al., 2008, Santegoets et al., 2008). Using DC migration from skin explants, Morelli et al. (2005) first reported that epidermal and dermal DC populations show similar mature phenotype and capacity to polarize alloreactive naive CD4 þ T cells into Th1 cells. The results are questionable, however, as these researchers defined LCs as the CD1a þ and DDCs as the CD1a À CD14 À migratory cell populations, whereas both DDCs and LCs are long known to express CD1a (Meunier et al., 1993; Nestle et al., 1993). "
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