Journal
JOURNAL OF IMMUNOLOGY
Volume 175, Issue 12, Pages 7905-7915Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.175.12.7905
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Funding
- NCI NIH HHS [R01CA100893] Funding Source: Medline
- NHLBI NIH HHS [R01HL075512, R21HL69725, R01HL077545] Funding Source: Medline
- NIAID NIH HHS [R01AI41011, AI51698, U01AI056488, R01AI06008, R21AI55027, R21AI57958] Funding Source: Medline
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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 CDla(+)CD14(-) Langerhans' cells (1,C), CDla(-)CD14(-) dermal DC (DDC), and CDla(-)CD14(+) 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 DO-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 11, adhesion, and costimulatory molecules. The Th1-biasing function of LC and DDC depended on their ability to produce IL-23. By contrast, CDla(-)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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