Abstract
The ability of human keratinocytes to present antigen to T cells is controversial and, indeed, it has been suggested that keratinocytes may promote T cell hyporesponsiveness. Furthermore, it is unclear whether keratinocytes can process antigen prior to MHC class I and class II presentation. We tested the ability of keratinocytes to induce functional responses in epitope-specific CD4+ and CD8+ memory T cells using peptides, protein and recombinant expression vectors as sources of antigen. Keratinocytes were able to efficiently process and present protein antigen to CD4+ T cells, resulting in cytokine secretion (Th1 and Th2). This interaction was dependent on keratinocyte expression of HLA class II and ICAM-1, which could be induced by IFN-gamma. In addition, keratinocytes could present virally encoded or exogenous peptide to CD8+ T cells, resulting in T cell cytokine production and target cell lysis. Finally, T cell lines grown using keratinocytes as stimulators showed no loss of function. These findings demonstrate that keratinocytes are able to efficiently process and present antigen to CD4+ and CD8+ memory T cells and induce functional responses. The findings have broad implications for the pathogenesis of cutaneous disease and for transcutaneous drug or vaccine delivery.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antibodies, Monoclonal / immunology
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Antibodies, Monoclonal / pharmacology
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Antigen Presentation / drug effects
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Antigen Presentation / immunology*
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Antigens, Dermatophagoides / immunology
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Arthropod Proteins
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B-Lymphocytes / immunology
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B7-1 Antigen / metabolism
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B7-2 Antigen / metabolism
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CD4-Positive T-Lymphocytes / cytology
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CD4-Positive T-Lymphocytes / immunology*
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CD4-Positive T-Lymphocytes / metabolism
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CD8-Positive T-Lymphocytes / cytology
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / metabolism
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Cell Line
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Cell Line, Transformed
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Cells, Cultured
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Cysteine Endopeptidases
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Cytotoxicity, Immunologic / drug effects
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Cytotoxicity, Immunologic / immunology
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HLA-D Antigens / metabolism
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Histocompatibility Antigens Class I / metabolism
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Humans
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Intercellular Adhesion Molecule-1 / metabolism
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Interferon gamma Receptor
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Interferon-gamma / metabolism
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Interferon-gamma / pharmacology
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Interleukin-4 / metabolism
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Keratinocytes / cytology
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Keratinocytes / immunology*
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Keratinocytes / metabolism
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Lymphocyte Function-Associated Antigen-1 / immunology
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Oligopeptides / immunology
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Parvovirus / immunology
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Phosphoproteins / immunology
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Receptors, Interferon / metabolism
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Trans-Activators / immunology
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Viral Proteins / immunology
Substances
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Antibodies, Monoclonal
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Antigens, Dermatophagoides
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Arthropod Proteins
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B7-1 Antigen
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B7-2 Antigen
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CD86 protein, human
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HLA-D Antigens
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Histocompatibility Antigens Class I
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Lymphocyte Function-Associated Antigen-1
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Oligopeptides
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Phosphoproteins
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Receptors, Interferon
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SM protein, Human herpesvirus 4
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Trans-Activators
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Viral Proteins
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glycyl-leucyl-cysteinyl-threonyl-leucyl-valyl-alanyl-methionyl-leucine
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Intercellular Adhesion Molecule-1
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Interleukin-4
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Interferon-gamma
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Cysteine Endopeptidases
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Dermatophagoides pteronyssinus antigen p 1