Psoriasis: a T-cell-mediated autoimmune disease induced by streptococcal superantigens?

Valdimarsson, H.; Baker, Barbara S.; Jónsdóttir, Ingileif; Powles, A.V.; Fry, Lionel

doi:10.1016/0167-5699(95)80132-4

Cited by 342 publications

(287 citation statements)

References 28 publications

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“…It has been shown that Th1 cells, characterized by interferon-gamma (IFN-g) production, are responsible for cell mediated immunity and inflammatory responses, while Th2 cells, characterized by IL-4, are involved in the switching of immunoglobulin M (IgM) to IgE and are associated with allergic diseases [30]. In psoriatic lesions, the Th1 type of cytokine pattern has been demonstrated [31,32], and accumulation of various cytokine-releasing T cell subsets in psoriatic epidermis may regulate the inflammatory process and keratinocyte hyperplasia [16]. T cell lines derived from psoriatic lesions were found to produce predominantly Th1-like cytokines [25], but a similar frequency of Th1-and Th2-like clones, with the majority of clones producing low amounts of both IFN-g and IL-4, has also been reported [33].…”

Section: Introductionmentioning

confidence: 99%

“…The principal objective of this project was to test the hypothesis that psoriatic lesions are caused and maintained by T lymphocytes that recognize amino acid sequences that are common to streptococcal M-proteins and human epidermal keratins [16]. To investigate the role of potentially cross-reactive T cells, M6-peptides sharing amino acid sequences with human epidermal keratins were identified and synthesized for analysis of T cell responses in psoriatic patients, healthy controls and patients with atopic dermatitis (AD).…”

Section: Introductionmentioning

confidence: 99%

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Circulating T Cells of Patients with Active Psoriasis Respond to Streptococcal M‐Peptides Sharing Sequences with Human Epidermal Keratins

et al. 1997

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Psoriasis is a T-cell mediated inflammatory skin disease which has been associated with group A, bhaemolytic streptococcal infections. Four 20 a.a. long M6-peptides sharing 5-6 a.a. sequences with human epidermal keratins were identified. To investigate the role of potentially cross-reactive T cells in the pathogenesis of psoriasis, interferon-g (IFN-g) and interleukin-4 (IL-4) responses of circulating T cells to these peptides were analysed by ELISPOT and RT-PCR in 14 psoriatic patients, 12 healthy individuals and six patients with atopic dermatitis (AD). Untreated psoriatic patients' responses were significantly higher to these peptides than healthy and AD controls, while responses to a control M6-peptide, not sharing sequences with keratin, were negligible in all groups. No difference was found in response to streptokinase/streptodornase (SK/SD). M6-protein and peptides exclusively elicited IFN-g production, with little IL-4 production, even in AD patients. Interferon-g responses to all the M6-peptides were abolished after successful treatment of psoriatic patients, but responses to SK/SD were unaffected. The results indicate that active psoriasis is associated with Th1-like cells responding to streptococcal M6-peptides sharing sequences with human epidermal keratin. This is consistent with the hypothesis that psoriasis may be induced and exacerbated in susceptible individuals by M-protein specific Th1-like cells that cross-react with human epidermal keratin.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Circulating T Cells of Patients with Active Psoriasis Respond to Streptococcal M‐Peptides Sharing Sequences with Human Epidermal Keratins

et al. 1997

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“…An immunologic basis, possibly triggered by staphylococcal or streptococcal superantigen, is suspected, but the event that initiates formation of the psoriatic plaque is unknown (Valdimarsson et al, 1995). Abnormal epithelial differentiation, extensive capillary formation in the papillary dermis, and accumulation of inflammatory leukocytes including T lymphocytes, NK lymphocytes, and granulocytes are also consistent features (Fry, 1988;Krueger et al, 1984;Malhotra et al, 1989;Mils et al, 1994).…”

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confidence: 99%

Anti-CD11a Ameliorates Disease in the Human Psoriatic Skin–SCID Mouse Transplant Model: Comparison of Antibody to CD11a with Cyclosporin A and Clobetasol Propionate

Zeigler

Chi

Tumas³

et al. 2001

Laboratory Investigation

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SUMMARY:The present study assesses the applicability of human skin-SCID (severe combined immunodeficiency) mouse chimeras in testing antipsoriatic therapeutics. Three agents were examined: (1) a monoclonal antibody to the alpha subunit of leukocyte function associated antigen-1 integrin (CD11a); (2) Cyclosporin A; and (3) clobetasol propionate (Temovate), a potent topical corticosteroid used clinically in the treatment of psoriasis. Skin transplanted to SCID mice from normal human volunteers or from psoriatic lesional skin was allowed to heal for 3 to 5 weeks before application of test reagents. During this period, psoriatic skin, which was 3.8-fold thicker than the corresponding normal skin before transplantation, maintained its phenotype (ie, increased epidermal thickness, rete ridges with blunted ends, and intralesional presence of T lymphocytes). Transplanted normal human skin, however, underwent a hyperplastic response during this period, resulting in a 2.4-fold increase in epidermal thickness. After the healing period, animals transplanted with normal or psoriatic skin were treated for 14 days by daily intraperitoneal injection of either Cyclosporin A or a monoclonal antibody to human CD11a, or by topical application of clobetasol propionate. At the end of the treatment period, the mice were killed and the tissue evaluated morphometrically for changes in epidermal thickness and immunohistologically for the presence of T lymphocytes. Both Cyclosporin A and anti-CD11a reduced the epidermal thickness of transplanted psoriatic skin, whereas neither reagent significantly reduced the thickness of transplanted normal skin. T lymphocytes were detected in the skin from treated animals; there did not seem to be any reduction in the number of T lymphocytes. Clobetasol propionate reduced the epidermal thickness of both normal and psoriatic skin. These data indicate that, in this model, therapies directed against pathophysiologic mechanisms that contribute to psoriasis can be distinguished from treatments that block epidermal hyperplasia occurring as a consequence of xenografting. Our observations provide evidence for the activity of anti-CD11a in an animal model of human psoriasis. (Lab Invest 2001, 81:1253-1261.

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“…For example, experimental autoimmune encephalomyelitis (EAE) is a rodent model of multiple sclerosis induced by immunizing with myelin basic protein (MBP) [1]. Although the involvement of autoimmunity is suggested in many inflammatory skin diseases, obvious autoantigens have not been found in most cases [2][3][4]. We have established a transgenic mouse (K5-mOVA) expressing ovalbumin (OVA) under a control of human keratin 5 promoter as a model skin autoantigen.…”

Section: Introductionmentioning

confidence: 99%

Prevention of toxic epidermal necrolysis by regulatory T cells

et al. 2005

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Psoriasis: a T-cell-mediated autoimmune disease induced by streptococcal superantigens?

Cited by 342 publications

References 28 publications

Circulating T Cells of Patients with Active Psoriasis Respond to Streptococcal M‐Peptides Sharing Sequences with Human Epidermal Keratins

Circulating T Cells of Patients with Active Psoriasis Respond to Streptococcal M‐Peptides Sharing Sequences with Human Epidermal Keratins

Anti-CD11a Ameliorates Disease in the Human Psoriatic Skin–SCID Mouse Transplant Model: Comparison of Antibody to CD11a with Cyclosporin A and Clobetasol Propionate

Prevention of toxic epidermal necrolysis by regulatory T cells

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