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

• Published in: Journal of Immunology Vol. 175; no. 12; pp. 7905 - 7915
• Main Authors: Morelli, Adrian E, Rubin, JPeter, Erdos, Geza, Tkacheva, Olga A, Mathers, Alicia R, Zahorchak, Alan F, Thomson, Angus W, Falo, Louis DJr, Larregina, Adriana T
• Format: Journal Article
• Language: English
• Published: 01.12.2005
• ISSN: 0022-1767; 1365-2567

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.