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Lymphocyte Isolation from Human Skin for Phenotypic Analysis and Ex Vivo Cell Culture
Published on: April 8, 2016
Stronger proliferative response to membrane versus cell-wall Streptococcal proteins by peripheral blood T cells in
B S Baker1, D Brown, V A Fischetti
1Department of Dermatology Faculty of Medicine, Imperial College of Science, Technology & Medicine, St Mary's Campus, London, UK. b.baker@ic.ac.uk
Abstract:
Proliferative responses of peripheral blood mononuclear cells (PBMC) to group A streptococcal (GAS) antigens have been studied in 24 patients with psoriasis and 15 disease controls. Extracts of cell wall (including M protein) from types M4 and M12 GAS, recombinant M6 protein, and both cell-wall and cell-membrane extracts from type M6 (M6+) GAS and its corresponding M gene deletion mutant (M6-) were tested. PBMC from psoriatic patients proliferated more strongly to cell-wall extracts from M12 versus M4 (P = 0.0348), and to M6+ versus M6- (P = 0.0019) GAS with, in most cases, moderate proliferation to recombinant M6 protein. The psoriatic response to M12 cell wall was significantly increased compared to the controls (P = 0.0032). In psoriatics, M6+ membrane extracts induced a markedly greater proliferation than those of cell wall (P = 0.0002); responses to M6+ (P = 0.0039) and M6- (P = 0.0114) membrane extracts were higher than those of the control PBMC. Both groups showed a decreased response to the M6- versus M6+ membrane extracts (P = 0.0030; P = 0.0181, respectively). This study has demonstrated that patients with psoriasis have a heightened circulating T-cell response to cell wall M protein and to non-M proteins present on the cell wall and membrane of GAS.
Insights
Patients with psoriasis exhibit an enhanced T-cell response to Group A Streptococcus (GAS) antigens, specifically M protein and other cell wall and membrane proteins. This heightened immune reactivity suggests a potential link between GAS and psoriasis pathogenesis.
Area of Science:
- Immunology
- Dermatology
- Microbiology
Background:
- Psoriasis is a chronic inflammatory skin condition with complex immune system involvement.
- Group A Streptococcus (GAS) has been implicated in triggering or exacerbating autoimmune and inflammatory diseases.
Purpose of the Study:
- To investigate the proliferative responses of peripheral blood mononuclear cells (PBMC) from psoriasis patients to various GAS antigens.
- To determine if psoriatic T-cells show a heightened reactivity to specific GAS components, including M protein and cell wall/membrane antigens.
Main Methods:
- Peripheral blood mononuclear cells (PBMC) from 24 psoriasis patients and 15 disease controls were isolated.
- PBMC were exposed to cell wall extracts (including M protein) from GAS types M4 and M12, recombinant M6 protein, and cell-wall/membrane extracts from M6+ GAS and its M gene deletion mutant (M6-).
- Proliferative responses were measured to assess T-cell reactivity to the different GAS antigens.
Main Results:
- Psoriatic PBMCs showed significantly stronger proliferation to M12 cell wall extracts compared to M4 GAS (P=0.0348) and to M6+ versus M6- GAS (P=0.0019).
- A markedly greater proliferation was observed in psoriatics in response to M6+ membrane extracts compared to cell wall extracts (P=0.0002).
- Responses to both M6+ and M6- membrane extracts were higher in psoriatics than in controls, indicating a general heightened response to membrane components.
Conclusions:
- Patients with psoriasis demonstrate a heightened circulating T-cell response to GAS cell wall M protein.
- There is also an increased T-cell reactivity to non-M proteins present on the cell wall and membrane of GAS in psoriatic individuals.
- These findings suggest a potential role for GAS antigens in the immune dysregulation observed in psoriasis.
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