Selective response of dermal Th-1 cells to 20-50 kDa streptococcal cell-wall proteins in chronic plaque psoriasis

We have recently described a dermal Th-1 subset in skin lesions of psoriasis which recognizes cell-wall extract isolated from group A streptococci (GAS). As a first step in the identification of the streptococcal proteins involved, dermal T-cell lines (TCL) cultured from the lesional skin of 12 human leucocyte antigen (HLA)-typed psoriasis patients were stimulated with GAS cell-wall extract and 14 fractions (MWt approximately 20-100 kDa) separated from the cell-wall extract by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and electroelution, stained for intracellular interferon-gamma (IFN-gamma) expression and analysed by flow cytometry. All the TCL responded to GAS cell-wall extract to varying extents (3.5-27.6% IFN-gamma(+)). This response was consistently directed against 20-50 kDa cell-wall fractions and inhibited by anti-HLA-DR antibody. TCL with higher responses to GAS cell-wall extract recognized a larger number of fractions within this range than the lower responder TCL. No difference between the level and pattern of response to the fractions was observed for TCL from HLA-DR7(+) (n = 6) and HLA-DR7(-) (n = 6) individuals. This preliminary study has shown a selective response to lower MWt proteins expressed on GAS cell wall by skin Th-1 cells in psoriasis. Further studies are required to identify the proteins involved.