title: CD1d-dependent, iNKT-cell cytotoxicity against keratinocytes in allergic contact dermatitis.
abstract: Conventional CD8+ T-lymphocytes are thought to be major effector cells in allergic contact dermatitis (ACD). However, previous work has demonstrated a significant population of invariant natural killer T-cells (iNKT-cells) in the elicitation phase of ACD. In this study, we investigate whether iNKT-cells have the capacity to serve as effector lymphocytes in ACD. Using in situ staining of skin biopsy specimens from ACD lesions, we observed intra-epidermal iNKT-cells. Presence of these cells provides the possibility of interactions with keratinocytes (KC), Langerhans cells (LC) and CD1d-bearing antigen-presenting cells (APC). Investigation into gene expression profiles of cytotoxic effector molecules in seven different cases of ACD found that the expression of perforin and granzymes A, B and K were significantly elevated in ACD relative to paired clinically normal skin. Immunostaining of ACD skin biopsy specimens revealed that these cytotoxic granules indeed localized to iNKT-cells. Studies of antigen presentation of KC to iNKT-cells show that these epithelial cells do not activate the expression of cytotoxicity effector genes in resting iNKT-cells, but had the capacity to serve as targets for activated iNKT-cells, which was dependent on CD1d expression. Mature LC were not able to present glycolipids to iNKT-cells and did not up-regulate CD1d in vitro to a variety of maturational stimuli or in vivo during ACD. These data suggest that iNKT-cells can serve as effector cells during human ACD and provide the rationale for developing inhibitory glycolipids as therapeutic agents for ACD.
authors.affiliation: Department of Dermatology, University of Naples Federico II School of Medicine, Naples, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Balato
authors.forename: Yuming
authors.initials: Y
authors.lastname: Zhao
authors.forename: Erin
authors.initials: E
authors.lastname: Harberts
authors.forename: Patricia
authors.initials: P
authors.lastname: Groleau
authors.forename: Juan
authors.initials: J
authors.lastname: Liu
authors.forename: Rita
authors.initials: R
authors.lastname: Fishelevich
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Gaspari
mesh_terms: D000328:Adult; D000368:Aged; D055610:Antigens, CD1d / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001706:Biopsy; D002450:Cell Communication / Q000276:immunology*; D002478:Cells, Cultured; D003594:Cytoplasmic Granules / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D017449:Dermatitis, Allergic Contact / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004817:Epidermis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005260:Female; D006017:Glycolipids / Q000276:immunology / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000276:immunology* / Q000473:pathology; D007801:Langerhans Cells / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000473:pathology; D010447:Peptide Hydrolases / Q000276:immunology / Q000378:metabolism; D054353:Perforin / Q000276:immunology / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D055610:Antigens, CD1d; C526877:CD1D protein, human; D006017:Glycolipids; D034741:RNA, Small Interfering; D054353:Perforin; D010447:Peptide Hydrolases