title: Non-M protein(s) on the cell wall and membrane of group A streptococci induce(s) IFN-gamma 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-gamma 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-gamma, 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-gamma+ 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-gamma in response to non-M protein(s) present on the cell wall and membrane of GAS.
authors.affiliation: Department of Dermatology, Imperial College of Science, Technology and Medicine at St Mary's, Paddington, London, UK.
authors.forename: D W
authors.initials: DW
authors.lastname: Brown
authors.forename: B S
authors.initials: BS
authors.lastname: Baker
authors.forename: J M
authors.initials: JM
authors.lastname: Ovigne
authors.forename: V A
authors.initials: VA
authors.lastname: Fischetti
authors.forename: C
authors.initials: C
authors.lastname: Hardman
authors.forename: A V
authors.initials: AV
authors.lastname: Powles
authors.forename: L
authors.initials: L
authors.lastname: Fry
mesh_terms: D000328:Adult; D000368:Aged; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002457:Cell Extracts / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D002473:Cell Wall / Q000378:metabolism; D017353:Gene Deletion; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D008565:Membrane Proteins / Q000502:physiology; D008875:Middle Aged; D009154:Mutation / Q000502:physiology; D011565:Psoriasis / Q000378:metabolism* / Q000382:microbiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D013297:Streptococcus pyogenes / Q000378:metabolism*
chemical_list: D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; D002457:Cell Extracts; D008565:Membrane Proteins; D011994:Recombinant Proteins; C014689:streptococcal M protein; D007371:Interferon-gamma