title: CD4+ T cell responses elicited by different subsets of human skin migratory dendritic cells.
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.
authors.affiliation: Department of Dermatology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
authors.forename: Adrian E
authors.initials: AE
authors.lastname: Morelli
authors.forename: J Peter
authors.initials: JP
authors.lastname: Rubin
authors.forename: Geza
authors.initials: G
authors.lastname: Erdos
authors.forename: Olga A
authors.initials: OA
authors.lastname: Tkacheva
authors.forename: Alicia R
authors.initials: AR
authors.lastname: Mathers
authors.forename: Alan F
authors.initials: AF
authors.lastname: Zahorchak
authors.forename: Angus W
authors.initials: AW
authors.lastname: Thomson
authors.forename: Louis D
authors.initials: LD
authors.lastname: Falo
authors.forename: Adriana T
authors.initials: AT
authors.lastname: Larregina
mesh_terms: D000938:Antigen-Presenting Cells / Q000276:immunology; D018949:Antigens, CD1; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002465:Cell Movement; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D007378:Interleukins / Q000096:biosynthesis; D018950:Lipopolysaccharide Receptors; D008213:Lymphocyte Activation / Q000276:immunology; D012867:Skin / Q000166:cytology* / Q000276:immunology; D018417:Th1 Cells; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D053773:Transforming Growth Factor beta1
chemical_list: D018949:Antigens, CD1; C419393:CD1a antigen; D007378:Interleukins; D018950:Lipopolysaccharide Receptors; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1