Human keratinocyte induction of rapid effector function in antigen-specific memory CD4+ and CD8+ T cells.
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.
Black
Antony P B
AP
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.
Ardern-Jones
Michael R
MR
Kasprowicz
Victoria
V
Bowness
Paul
P
Jones
Louise
L
Bailey
Abigail S
AS
Ogg
Graham S
GS
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology*; D039741:Antigens, Dermatophagoides / Q000276:immunology; D060829:Arthropod Proteins; D001402:B-Lymphocytes / Q000276:immunology; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000276:immunology; D006681:HLA-D Antigens / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology; D015847:Interleukin-4 / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology; D009842:Oligopeptides / Q000276:immunology; D017992:Parvovirus / Q000276:immunology; D010750:Phosphoproteins / Q000276:immunology; D017471:Receptors, Interferon / Q000378:metabolism; D015534:Trans-Activators / Q000276:immunology; D014764:Viral Proteins / Q000276:immunology; D000096743:Interferon gamma Receptor
D000911:Antibodies, Monoclonal; D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D003546:Cysteine Endopeptidases; D006681:HLA-D Antigens; D015395:Histocompatibility Antigens Class I; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D015847:Interleukin-4; D016169:Lymphocyte Function-Associated Antigen-1; D009842:Oligopeptides; D010750:Phosphoproteins; D017471:Receptors, Interferon; D015534:Trans-Activators; D014764:Viral Proteins; D000096743:Interferon gamma Receptor; C497964:CD86 protein, human; C090236:SM protein, Human herpesvirus 4; C403195:glycyl-leucyl-cysteinyl-threonyl-leucyl-valyl-alanyl-methionyl-leucine; C451162:Dermatophagoides pteronyssinus antigen p 1