Reduced IFN-γ 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-γ 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-R15 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 streptococci.