Bacterial superantigen facilitates epithelial presentation of allergen to T helper 2 cells.
Although clinical and laboratory evidence support roles for both staphylococcal infection and environmental allergens in the pathogenesis of atopic dermatitis, human studies have largely considered these variables independently. We sought to test the hypothesis that staphylococcal superantigen influences the allergen-specific T cell response. We first mapped a Der p 1 epitope and used HLA DRB1*1501 class II tetramer-based cell sorted populations to show that specific CD4(+) T cells were able to recognize the peptide presented by HLA DR-matched keratinocytes. We observed that staphylococcal enterotoxin B (SEB) enhanced the IL-4 Der p 1-specific T cell response. This response was mediated by two synergistic mechanisms: first, SEB-induced IFN-gamma promoted class II and intercellular adhesion molecule-1 expression by presenting keratinocytes; and second, SEB-induced IL-4 directly amplified allergen-specific CD4(+) T cell production of many cytokines. We propose that handling of staphylococcal infection is a critical step in the amplification of the allergen-specific T cell response, linking two common disease associations and with implications for the prevention and treatment of atopic disease.
Ardern-Jones
Michael R
MR
Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.
Black
Antony P
AP
Bateman
Elizabeth A
EA
Ogg
Graham S
GS
D000485:Allergens; D000938:Antigen-Presenting Cells; D000942:Antigens, Bacterial / Q000378:metabolism / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000382:microbiology; D004847:Epithelial Cells / Q000166:cytology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000382:microbiology; D008213:Lymphocyte Activation; D010455:Peptides / Q000737:chemistry; D018418:Th2 Cells / Q000166:cytology* / Q000382:microbiology*
D000485:Allergens; D000942:Antigens, Bacterial; D018925:Chemokines; D010455:Peptides; D015847:Interleukin-4; D007371:Interferon-gamma