Reduced IFN-gamma responses associated with HLA-DR15 presentation of streptococcal cell wall proteins to dermal Th-1 cells in psoriasis.
We have recently described a group A streptococcal (GAS)-reactive Th-1 subset specifically present in skin lesions of chronic plaque psoriasis. To investigate MHC presentation of GAS cell wall proteins, dermal T cell lines (TCL) cultured from the lesional skin of 39 HLA-typed psoriasis patients were stimulated with a cell wall extract, stained for intracellular IFN-gamma expression, and analyzed by flow cytometry. TCL from a further seven psoriasis patients were also tested with S. mutans extract. Eight TCL were tested in the presence of anti-Class II antibodies or allogeneic antigen-presenting cells. The dermal T cell IFN-gamma responses to the cell wall extract, which ranged from < 1 to 28%, were significantly higher than that to S. mutans extract (p = 0.0052) and were self-HLA-DR allele restricted. A significantly decreased response was observed in TCL from DR15+ (n = 13) versus DR15- (n = 26) patients (p = 0.0377). In addition, DR15+ patients had a later age of onset of disease and a decreased history of sore throats. In contrast, TCL from HLA-DR7+ (n = 23) patients responded similarly to those from individuals lacking the DR7 allele. However, DR7+ patients who coexpressed the MHC Class I antigen, Cw6 (n = 14) had a significantly higher IFN-gamma response than Cw6-, DR7+ patients (n = 7; p = 0.0288) whose responses were also significantly lower than those of patients expressing non-DR7 alleles (n = 16; p = 0.0302). This study has shown that HLA-DR15 expression is associated with a reduced dermal Th-1 response to GAS cell wall proteins in patients with psoriasis. It is proposed that HLA-DR allelic variation may contribute to disease phenotype via effects on the immune response to group A streptococci.
Department of Dermatology, Faculty of Medicine, Imperial College of Science, Technology & Medicine, London, United Kingdom. b.baker@imperial.ac.uk
Barbara S
BS
Baker
Jean-Marc
JM
Ovigne
Vincent A
VA
Fischetti
Anne
A
Powles
Lionel
L
Fry
D000328:Adult; D017668:Age of Onset; D000368:Aged; D017951:Antigen Presentation; D001426:Bacterial Proteins / Q000276:immunology; D002457:Cell Extracts / Q000276:immunology; D002473:Cell Wall / Q000737:chemistry / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D005802:Genes, MHC Class II / Q000235:genetics; D015236:HLA-C Antigens / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology*; D059810:HLA-DR Serological Subtypes; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010612:Pharyngitis / Q000235:genetics / Q000276:immunology; D011565:Psoriasis / Q000276:immunology*; D012867:Skin / Q000276:immunology*; D013291:Streptococcus / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*
D001426:Bacterial Proteins; D002457:Cell Extracts; D015236:HLA-C Antigens; C528994:HLA-C*06 antigen; D006684:HLA-DR Antigens; D059810:HLA-DR Serological Subtypes; C106559:HLA-DR15 antigen; D007371:Interferon-gamma