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

• Published in: The Journal of immunology (1950) 2004-01, Vol.172 (2), p.857-863
• Main Authors: Dudda, Jan C, Simon, Jan C, Martin, Stefan
• Format: Article
• Language: English
• Subjects: Adoptive Transfer; Animals; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - pathology; Cell Movement - immunology; Chemokines, CC - metabolism; Dendritic Cells - immunology; Dendritic Cells - pathology; Dendritic Cells - transplantation; Dermatitis, Contact - immunology; Dermatitis, Contact - pathology; Immunologic Memory; Inflammation - immunology; Injections, Intradermal; Injections, Intravenous; Membrane Glycoproteins - biosynthesis; Mice; Mice, Inbred C57BL; Mice, Transgenic; Organ Specificity - immunology; Picryl Chloride - administration & dosage; Picryl Chloride - immunology; Receptors, CCR4; Receptors, Chemokine - biosynthesis; Receptors, Fibroblast Growth Factor - biosynthesis; Sialoglycoproteins; Skin - immunology; Skin - pathology; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; T-Lymphocyte Subsets - pathology; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.172.2.857

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.