title: T-lymphocyte-induced, Fas-mediated apoptosis is associated with early keratinocyte differentiation.
abstract: The development of eczematous lesions is thought to be due in part to a breakdown in skin barrier function as a result of T lymphocytes (T cells) invading the skin causing epidermal keratinocyte apoptosis. In this study, we investigated the interaction of T cells and keratinocytes on apoptosis and terminal differentiation using an in vitro co-culture system. Experiments were performed using the HaCaT keratinocyte cell line or normal human epidermal keratinocytes. Activated human peripheral blood-derived T cells were found to induce Fas-dependent keratinocyte apoptosis by up to sixfold. Increased Fas was associated with increased IFN-gamma. The T-cell apoptotic signal was found to target preferentially keratinocytes in the very early stages of terminal differentiation, such as those with low levels of alpha 6-integrin expression, and result in subsequent increased caspase 3 activity. This observation was accompanied by a marked increase in keratinocyte ICAM-1 expression and its ligand LFA-1 on T cells. Our data suggest that T cells may initiate the onset of keratinocyte terminal differentiation making them more susceptible to Fas-dependent cell death signals delivered by the T cells.
authors: Women's & Children's Health Research Institute, Women's and Children's Hospital, North Adelaide, SA, Australia. ilse.daehn@cancer.org.uk
authors: Ilse S
authors: IS
authors: Daehn
authors: Antiopi
authors: A
authors: Varelias
authors: Timothy E
authors: TE
authors: Rayner
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D061945:Caspase Inhibitors; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology*; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D018920:Coculture Techniques; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D053222:Fas Ligand Protein / Q000378:metabolism; D006801:Humans; D039503:Integrin alpha6 / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology; D053550:Keratin-10 / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019014:fas Receptor / Q000276:immunology / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; C491901:FAS protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D039503:Integrin alpha6; C507493:KRT10 protein, human; D016169:Lymphocyte Function-Associated Antigen-1; D009842:Oligopeptides; D011498:Protein Precursors; D014409:Tumor Necrosis Factor-alpha; C110922:acetyl-aspartyl-methionyl-glutaminyl-aspartyl-aldehyde; D019014:fas Receptor; D018799:Intercellular Adhesion Molecule-1; D053550:Keratin-10; D015759:Ionomycin; C032253:involucrin; D007371:Interferon-gamma; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D013755:Tetradecanoylphorbol Acetate