CD4 super(+) T Cell Responses Elicited by Different Subsets of Human Skin Migratory Dendritic Cells
Skin dendritic cells (DC) are professional APC critical for initiation and control of adaptive immunity. In the present work we have analyzed the CD4 super(+) T cell stimulatory function of different subsets of DC that migrate spontaneously from human skin explants, including CD1a super(+)CD14 super...
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Published in | Journal of Immunology Vol. 175; no. 12; pp. 7905 - 7915 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
01.12.2005
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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 super(+) T cell stimulatory function of different subsets of DC that migrate spontaneously from human skin explants, including CD1a super(+)CD14 super(-) Langerhans' cells (LC), CD1a super(-)CD14 super(-) dermal DC (DDC), and CD1a super(-)CD14 super(+) LC precursors. Skin migratory DC consisted of APC at different stages of maturation-activation that produced IL-10, TGF- beta 1, 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 super(+) T cells and to induce memory Th1 cells in the absence of IL-12p70. The potent CD4 super(+) 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 super(-)CD14 super(+) LC precursors migrated as immature-semimature APC and were weak stimulators of allogeneic naive CD4 super(+) T cells. However, and opposite of a potential tolerogenic role of immature DC, the T cell allostimulatory and Th1-biasing function of CD14 super(+) 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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AbstractList | Skin dendritic cells (DC) are professional APC critical for initiation and control of adaptive immunity. In the present work we have analyzed the CD4 super(+) T cell stimulatory function of different subsets of DC that migrate spontaneously from human skin explants, including CD1a super(+)CD14 super(-) Langerhans' cells (LC), CD1a super(-)CD14 super(-) dermal DC (DDC), and CD1a super(-)CD14 super(+) LC precursors. Skin migratory DC consisted of APC at different stages of maturation-activation that produced IL-10, TGF- beta 1, 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 super(+) T cells and to induce memory Th1 cells in the absence of IL-12p70. The potent CD4 super(+) 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 super(-)CD14 super(+) LC precursors migrated as immature-semimature APC and were weak stimulators of allogeneic naive CD4 super(+) T cells. However, and opposite of a potential tolerogenic role of immature DC, the T cell allostimulatory and Th1-biasing function of CD14 super(+) 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. |
Author | Thomson, Angus W Zahorchak, Alan F Falo, Louis DJr Erdos, Geza Mathers, Alicia R Larregina, Adriana T Tkacheva, Olga A Morelli, Adrian E Rubin, JPeter |
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Title | CD4 super(+) T Cell Responses Elicited by Different Subsets of Human Skin Migratory Dendritic Cells |
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