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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.

Original publication

DOI

10.1002/eji.200636915

Type

Journal article

Journal

Eur J Immunol

Publication Date

06/2007

Volume

37

Pages

1485 - 1493

Keywords

Antibodies, Monoclonal, Antigen Presentation, Antigens, Dermatophagoides, Arthropod Proteins, B-Lymphocytes, B7-1 Antigen, B7-2 Antigen, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cell Line, Cell Line, Transformed, Cells, Cultured, Cysteine Endopeptidases, Cytotoxicity, Immunologic, HLA-D Antigens, Histocompatibility Antigens Class I, Humans, Intercellular Adhesion Molecule-1, Interferon-gamma, Interleukin-4, Keratinocytes, Lymphocyte Function-Associated Antigen-1, Oligopeptides, Parvovirus, Phosphoproteins, Receptors, Interferon, Trans-Activators, Viral Proteins