Characterization of T-cell clones generated from skin of patients with psoriasis

Nikaein, Afzal; Morris, Lynn; Phillips, Charles M.; Soliman, Mosaad; Ordonez, Guido; Silverman, Alan K.; Stone, Marvin J.; Menter, Alan

doi:10.1016/0190-9622(93)70073-3

Cited by 16 publications

(4 citation statements)

References 40 publications

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“…While in both circumstances PP skin-derived DDCs and blood-derived DDCs did stimulate autologous T cell proliferation (confirming the existence of circulating autoreactive T cells) (5)(6)(7)18), the skin -derived DDCs were always capable of greater T cell stimulation compared with blood-derived DDCs using the same individual T cells as responders. Thus, these results suggest that PP skin-derived DDCs may also bear T cell mitogenic signals beyond HLA-DR and B7.…”

Section: Discussionmentioning

confidence: 78%

Characterization of dermal dendritic cells in psoriasis. Autostimulation of T lymphocytes and induction of Th1 type cytokines.

Nestle

Turka²,

Nickoloff³

1994

J. Clin. Invest.

273

167

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Introduction Psoriasis is a common, well-defined skin disease featuring the interplay of genetic, environmental, and immunological factors (1). Psoriasis is listed among other chronic diseases believed to be of autoimmune origin, such as multiple sclerosis (2). While it shares clinical features with multiple sclerosis such as spontaneous remissions and exacerbations, the cellular and molecular basis for targeting T cell involvement in the skin remains unknown (2). Unlike multiple sclerosis in which a specific "antigen" has been identified (i.e., myelin basic protein) and a reproducible animal model exists (i.e., experimental allergic encephalitis), psoriasis research has been hampered by the absence of an identifiable self-antigen or animal model. Perhaps the strongest evidence supporting an autoimmune basis for psoriasis are reports that eradication of a psoriatic patient's bone marrow, and replacement with a genetically different nonpsoriatic donor, can completely cure the skin lesions (3, 4).The predominant investigative pathway into autoimmunity and psoriasis has primarily been in the direction of studies of T lymphocytes (5-7), with little or no regard for the potential importance of the antigen-presenting cell populations in the dermis that possess a dendritic morphology. Members of the dendritic cell system possess an extremely potent capacity to stimulate resting T cell proliferation and cytokine release (8)(9)(10). Rather than focusing on T cells, we asked whether dendritic cells isolated from skin of active untreated psoriatic lesions possess the capability of stimulating resting, autologous peripheral blood T cells. Dermal dendritic cells (DDCs)' are increased in psoriatic lesions (11, 12), and we pointed out previously the potential importance of dendritic cell/T cell interaction in the pathophysiology of psoriasis ( 13). To determine whether psoriatic plaque (PP) DDCs possessed the capacity to stimulate spontaneous proliferation of autologous T cells, a method for isolating DDCs from both PP and normal skin (NN) was devised. Comparisons were made between such skin-derived as well as psoriatic blood-derived dendritic cells in autologous T cell proliferation assays measured with and without the addition of other T cell mitogenic stimuli such as bacterialderived superantigens (SA) (staphylococcal enterotoxins A and B) and PHA. Studies involving superantigens were included because bacterial infections are frequent triggering factors for psoriatic lesion formation, and superantigens have been implicated in the pathogenesis of psoriasis ( 1,14). Our data indicate that PP DDCs do possess a potent autostimulatory capacity to induce proliferation of resting T cells which is mediated by involvement of HLA-DR, B7, and lymphocyte function associated antigen-I (LFA-1) molecules and associated with high 1. Abbreviations used in this paper: DDCs, dermal dendritic cells; LFA-1, lymphocyte function associated antigen-l; NN, normal skin; PP, psoriatic plaques; SA, superantigens.

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Section: Discussionmentioning

confidence: 78%

Characterization of dermal dendritic cells in psoriasis. Autostimulation of T lymphocytes and induction of Th1 type cytokines.

Nestle

Turka²,

Nickoloff³

1994

J. Clin. Invest.

273

167

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“…1 The predominance of T lymphocytes in the non-tumorigenic lesions concurs previous studies. 12,13 These T lymphocytes may be activated in these lesions by bacterial superantigens. 10,14,15 Cytotoxic T-lymphocytes (CTLs) are able to recognize and destroy tumor cells through the release of cytoplasmic granules, which contain TIA-1.…”

Section: Discussionmentioning

confidence: 99%

Analysis of the mononuclear inflammatory cell infiltrate in the nontumorigenic, Pretumorigenic and tumorigenic keratinocytic hyperproliferative lesions of the skin

Hussein¹,

Ahmed²

2005

Cancer Biology & Therapy

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Background: The keratinocytic hyperproliferative lesions include non-tumorigenic, pre-tumorigenic (actinic keratoses, AK), and tumorigenic (squamous cell carcinomas, SCC) conditions. Although mononuclear inflammatory cell infiltrate (MICs) is a constant feature in these lesions, their immunophenotypic characterization is still incomplete. We hypothesized that the development of non-tumorigenic, pre-tumorigenic, and tumorigenic keratinocytic hyperproliferative lesions is associated with alterations in the mononuclear inflammatory cell infiltrate in response to altered antigenicity of the lesional cells. This study tries to test this hypothesis and to characterize MICs in these lesions.Methods: Fifty lesions (non-tumorigenic lesions, 29; AK, 9 and SCC, 12) were examined using immunoperoxidase staining methods and antibodies targeting histiocytes (CD68), T cells (CD3), B cells (CD20), and T cells with cytotoxic potential (TIA-1).Results: As compared to the normal skin, the development of the keratinocytic hyperproliferative lesions (normal skin; non-tumorigenic; AK and SCC) was associated with a statistically significant increase(p = <0.05) in: (1) CD20 + B lymphocytes (0.0 ± 0.0 vs. 3.1 ± 0.5 vs. 7.5 ± 0.3 vs. 14.5 ± 5.5); (2) CD68 histiocytes (4.0 ± 1.0 vs. 26.5 ± 3.9 vs. 23 ± 1.9 vs. 41.3 ± 6.8); (3) CD3 + T lymphocytes (3.0 ± 1.1 vs. 58.3 ± 10.3 vs. 54.5 ± 0.2 vs. 41.0 ± 16.0); and (4) TIA-1 + cytotoxic T cells (1.8 ± 0.4 vs. 2.9 ± 0.7 vs. 9.6 ± 1.1 vs. 13.7 ± 5.2).Conclusions: The increase in the number of infiltrating mononuclear cells in all pathologic lesions compared to normal skin may reflect increased antigenicity of the lesional cells. Both humoral and cell mediated immunity are involved in these lesions.

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“…T cell clones T lymphocytes from a lesional skin biopsy of a patient with severe psoriasis ( ^ 50% body surface area involvement) were expanded in culture as described previously [17,18]. The biopsy was divided into small fragments and placed in RPMI 1640 (GIBCO, Grand Island, NY) supplemented with gentamicin, human AB serum and 25% purified human IL-2 (Boehringer Mannheim, Indianapolis, IN).…”

Section: Biopsiesmentioning

confidence: 99%

IL-8/IL-8 receptor expression in psoriasis and the response to systemic tacrolimus (FK506) therapy

Lemster

Carroll

Rilo

et al. 1995

Clinical and Experimental Immunology

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SUMMARY Recently, the keratinocyte IL‐8/IL‐8 receptor (IL‐8R) pathway has been implicated in the pathogenesis of psoriasis, and there is evidence that the potent macrolide immune suppressant tacrolimus (formerly FK506) can inhibit this pathway in vitro. In this study, determination of the expression of cytokine mRNAs in lesional skin of patients with active disease by reverse transcriptase polymerase chain reaction revealed transcripts for IL‐1β, tumour necrosis factor‐alpha (TNF‐α), IL‐6, IL‐8, IL‐8R, IL‐10, interferon‐gamma (IFN‐γ), IL‐2R and transforming growth factor‐beta (TGF‐β), but not IL‐2 or IL‐4. IL‐8 was the only cytokine expressed in affected skin of all patients but not in clinically normal skin of healthy subjects. In seven CD4+ T cell clones propagated from the lesional skin of an untreated psoriasis patient, IL‐8 was expressed by the skin‐derived T lymphocytes and not by feeder cells (irradiated autologous blood lymphocytes); IL‐1β, IL‐2, IL‐6 and IL‐10 were also expressed by some or all of the T cell clones, IL‐8 mRNA was not detected in the skin of any patient after the start of systemic tacrolimus therapy; IL‐lβ, IL‐6 and IFN‐γ transcripts were also reduced. By 12 weeks, the mean psoriasis area and severity index (PASI) had decreased from 18·8 to 3·8, a reduction of 80%. In the same post‐treatment biopsies, however, message for IL‐8R persisted. Estimation of circulating IL‐8 levels by enzyme immunoassay showed that all patients with detectable IL‐8 before treatment had decreased levels in response to treatment with tacrolimus; reductions in PASI scores were accompanied by decreases in IL‐8 levels, that varied both in rate and extent. Partial relapse, which in a minority of patients followed the initial period of remission, and was precipitated by drug dose reduction, was accompanied by an increase in circulating IL‐8. These findings add credence to the view that the IL‐8/IL‐8R autocrine/paracrine pathway may be important in the pathogenesis of psoriasis. They further suggest that interference with IL‐8 production and/or that of other key chemokines may be an important mechanism underlying the therapeutic efficacy of tacrolimus, and other agents such as cyclosporin A, with similar molecular actions.

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Characterization of T-cell clones generated from skin of patients with psoriasis

Cited by 16 publications

References 40 publications

Characterization of dermal dendritic cells in psoriasis. Autostimulation of T lymphocytes and induction of Th1 type cytokines.

Characterization of dermal dendritic cells in psoriasis. Autostimulation of T lymphocytes and induction of Th1 type cytokines.

Analysis of the mononuclear inflammatory cell infiltrate in the nontumorigenic, Pretumorigenic and tumorigenic keratinocytic hyperproliferative lesions of the skin

IL-8/IL-8 receptor expression in psoriasis and the response to systemic tacrolimus (FK506) therapy

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