Dendritic cell immunization route determines CD8+ T cell trafficking to inflamed skin: role for tissue microenvironment and dendritic cells in establishment of T cell-homing subsets.
The effector/memory T cell pool branches in homing subsets selectively trafficking to organs such as gut or skin. Little is known about the critical factors in the generation of skin-homing CD8+ T cells, although they are crucial effectors in skin-restricted immune responses such as contact hypersensitivity and melanoma defense. In this study, we show that intracutaneous, but not i.v. injection of bone marrow-derived dendritic cells induced skin-homing CD8+ T cells with up-regulated E-selectin ligand expression and effector function in contact hypersensitivity. The skin-homing potential and E-selectin ligand expression remained stable in memory phase without further Ag contact. In contrast, i.p. injection induced T cells expressing the gut-homing integrin alpha(4)beta(7). Although differential expression of these adhesion molecules was strictly associated with the immunization route, the postulated skin-homing marker CCR4 was transiently up-regulated in all conditions. Interestingly, dendritic cells from different tissues effectively induced the corresponding homing markers on T cells in vitro. Our results suggest a crucial role for the tissue microenvironment and dendritic cells in the instruction of T cells for tissue-selective homing and demonstrate that Langerhans cells are specialized to target T cells to inflamed skin.
Dudda
Jan C
JC
Clinical Research Group Allergology, Department of Dermatology, University of Freiburg, Hauptstrasse 7, D-79104 Freiburg, Germany.
Simon
Jan C
JC
Martin
Stefan
S
D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement / Q000276:immunology*; D019742:Chemokines, CC / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology / Q000637:transplantation*; D003877:Dermatitis, Contact / Q000276:immunology / Q000473:pathology; D007156:Immunologic Memory; D007249:Inflammation / Q000276:immunology; D007271:Injections, Intradermal; D007275:Injections, Intravenous; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009928:Organ Specificity / Q000276:immunology; D010853:Picryl Chloride / Q000008:administration & dosage / Q000276:immunology; D054398:Receptors, CCR4; D019707:Receptors, Chemokine / Q000096:biosynthesis; D017468:Receptors, Fibroblast Growth Factor / Q000096:biosynthesis; D012795:Sialoglycoproteins; D012867:Skin / Q000276:immunology* / Q000473:pathology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism
C515355:Ccr4 protein, mouse; D019742:Chemokines, CC; D008562:Membrane Glycoproteins; D054398:Receptors, CCR4; D019707:Receptors, Chemokine; D017468:Receptors, Fibroblast Growth Factor; D012795:Sialoglycoproteins; C086711:cysteine-rich fibroblast growth factor receptor; D010853:Picryl Chloride