Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 37, Issue 6, Pages 1485-1493Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/eji.200636915
Keywords
antigen presentation; keratinocytes; skin
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Funding
- Medical Research Council [G116/150, MC_U137881017, MC_U137884185] Funding Source: Medline
- Medical Research Council [MC_U137881017, MC_U137884185, G116/150] Funding Source: researchfish
- MRC [MC_U137884185, MC_U137881017, G116/150] Funding Source: UKRI
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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(+) memoryTcells usingpeptides, 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-7. 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.
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