Non-M protein(s) on the cell wall and membrane of group A streptococci induce(s) IFN-γ production by dermal CD4⁺ T cells in psoriasis

Abstract Recently we have demonstrated that a disease-specific subpopulation of CD4⁺ T cells isolated from skin lesions of chronic plaque psoriasis produces interferon-γ in response to group A streptococcal (GAS) antigens. To determine if these T cells recognize M or non-M protein, extracts from cell wall of type M6 GAS (M6W) and its isogenic M gene deletion mutant (M-W), M6 membrane extract (M6M) and recombinant M6 protein (rM6) were used to stimulate GAS-reactive T-cell lines from nine patients with chronic plaque psoriasis. T-cell lines were incubated with or without streptococcal extracts for 18 h in the presence of a transport inhibitor, stained for surface CD4 and intracellular cytokine expression, and analysed by flow cytometry. Variable numbers (0.2–34%) of CD4⁺ T cells produced interferon-γ, in all but one of the T-cell lines tested, in response to M6W, M-W and M6M extracts. No significant difference between the response to M6W and M-W extracts was detected. In addition, rM6 protein failed to increase CD4⁺/interferon-γ⁺ T-cell numbers in seven of nine T-cell lines compared to medium alone. For the group, there was a highly significant correlation between the responses to the three extracts (M6W vs M-W, P = 0.0005; M6W vs M6M, P = 0.0003; M-W vs M6M, P = 0.0001). Low or minimal numbers of interleukin-4- and interleukin-10-producing CD4⁺ T cells were occasionally induced. These findings suggest that a subpopulation of CD4⁺ T cells isolated from skin lesions of chronic plaque psoriasis patients produces interferon-γ in response to non-M protein(s) present on the cell wall and membrane of GAS.