Evidence of HLA-DR antigen biosynthesis by human keratinocytes in disease.

Volc‐Platzer, Beatrix; Majdic, Otto; Knapp, Walter; Wolff, Klaus; Hinterberger, W; Lechner, Kristina; Stingl, Georg

doi:10.1084/jem.159.6.1784

Cited by 162 publications

(41 citation statements)

References 18 publications

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“…This was also confirmed by staining keratinocytes obtained by suction blister induction. Thus, psoriasis should be added to an increasing list of dermatoses in which HLA-DR' keratinocytes are present (16)(17)(18)(19). In this context, the failure of other investigators to find HLA-DR' keratinocytes in psoriatic plaques needs further explanation .…”

Section: Discussionmentioning

confidence: 99%

“…Under various pathologic conditions, HLA-DR has been detected on keratinocytes in involved skin (16)(17)(18)(19). Studies of human delayed-type hypersensitivity reactions in vivo have shown keratinocyte HLA-DR expression at only restricted times during the course of the response (33).…”

Section: Discussionmentioning

confidence: 99%

“…In normal skin, HLA-DR expression is confined to Langerhans cells with Birbeck granules (12,13), indeterminate cells without Birbeck granules (13), and acrosyringeal epithelium (14,15) . HLA-DR expression by keratinocytes has been reported (16)(17)(18)(19) in several human dermatoses characterized by mononuclear infiltrates . In the case of psoriasis, a recent study (20) reported the focal expression of HLA-DR antigens in epidermal cells .…”

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confidence: 99%

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Expression of HLA-DR molecules by keratinocytes, and presence of Langerhans cells in the dermal infiltrate of active psoriatic plaques.

Gottlieb¹,

Lifshitz²,

Fu³

et al. 1986

The Journal of Experimental Medicine

190

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Immunoperoxidase staining of skin sections and immunofluorescence analysis of keratinocyte suspensions obtained from suction blisters of psoriatic plaques were performed using an mAb, Josh 524.4.1, and Fab'2 fragments of a rabbit antiserum, both of which are directed against nonpolymorphic determinants of HLA-DR molecules. HLA-DR+ keratinocytes were present in plaques, but not normal-appearing skin, from a significant portion of patients with active psoriasis. Double-labelling immunofluorescence experiments with either the monoclonal or polyclonal anti-HLA-DR antibody, in conjunction with the mAb OKT6, which identifies DR+ Langerhans cells, demonstrated that HLA-DR molecules were present on OKT6- keratinocytes. The dermal infiltrate of psoriatic plaques contained T cells expressing the activation antigens, IL-2 receptor (Tac) and HLA-DR, as well as macrophages and OKT6+ cells. There was little difference in the characteristics of the dermal infiltrate between the lesions with or without HLA-DR+ keratinocytes. OKT6+ presumptive Langerhans cells were also found in the dermal infiltrates of patients with lichen planus, contact dermatitis, spongiotic dermatitis, erythema multiforme, basal and squamous cell carcinoma. Studies of keratinocyte suspensions showed that 7-84% of keratinocytes were HLA-DR+. Flow cytometry experiments showed that keratinocytes at all stages of differentiation were HLA-DR+. However, the stem cell-enriched population contained the highest proportion of HLA-DR+ cells. HLA-DR expression by keratinocytes correlated with disease activity. The expression was reversible with successful medical therapy. HLA-DR+ keratinocytes may activate T cells directly or may present an as yet unknown antigen to T cells. These studies provide further support for the hypothesis that immunological mechanisms play an important role in the pathogenesis of psoriasis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Expression of HLA-DR molecules by keratinocytes, and presence of Langerhans cells in the dermal infiltrate of active psoriatic plaques.

Gottlieb¹,

Lifshitz²,

Fu³

et al. 1986

The Journal of Experimental Medicine

190

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“…In tissue samples from 3 of our 15 patients, anti-class II reagents produced diffuse staining; however, in the epithelial cells from the other 12 patients, the test results were negative. It is possible that chronic environmental or microbiologic factors leads to class II antigen expression by pulmonary tissues in a manner similar to that seen in keratinocytes in certain diseases (33).…”

Section: Discussionmentioning

confidence: 99%

Dendritic cells with antigen-presenting capability reside in airway epithelium, lung parenchyma, and visceral pleura.

Sertl¹,

Takemura²,

Tschachler³

et al. 1986

The Journal of Experimental Medicine

340

184

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In this study, we identified a population of dendritic cells (DC) that exists throughout human and mouse pulmonary tissues, including the trachea, bronchi, alveoli, and visceral pleura. In human tissue, these DC were shown to be positive for HLA-DR and T200 antigens. In the mouse, the DC expressed not only Ia and the T200 antigen, but also Fc-IgG and C3bi receptors. Unlike alveolar macrophages, the DC were negative for nonspecific esterase staining and shared ultrastructural similarities with the DC described by Steinman (1), and with Langerhans' cells, even though they did not contain Birbeck granules. We were able to demonstrate that mouse pulmonary DC function in antigen presentation, as observed with the other DC. Thus, the respiratory tract contains DC that are capable of functioning in antigen presentation and that may be important in pulmonary immune responses.

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“…HLA-DR+ KTCs were not found in the skin of 3 normal individuals (5). Although HLA-DR+ KTCs have been demonstrated in certain diseases (5,(30)(31)(32)(33), they were not found in normal-appearing skin from patients with rheumatoid arthritis, osteoarthritis, advanced scleroderma, subacute cutaneous lupus erythematosus, or dermatomyositis (5).…”

Section: Resultsmentioning

confidence: 99%

Marked increase in the frequency of psoriatic arthritis in psoriasis patients with hla–dr+ keratinocytes

Gottlieb

Carter

et al. 1987

Arthritis & Rheumatism

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Immunocytochemical studies with a monoclonal anti–HLA–DR antibody were performed on skin sections and keratinocyte (KTC) suspensions obtained from suction blisters of active psoriatic plaques. HLA–DR+ KTCs were found in the plaques of 23 of 38 patients with active psoriasis. Of these 23, 16 had clinical findings typical of psoriatic arthritis (PA); none of the 15 patients who lacked HLA–DR+ KTCs had PA. Although KTC HLA–DR expression was more prevalent in patients with severe skin disease, 7 of the 23 patients with HLA–DR + KTCs in active psoriatic plaques had mild skin disease; 4 of these 7 had PA. Nail pitting or duration of skin disease did not account for increased incidence of PA in patients with HLA–DR+ KTCs. All psoriasis patients with arthritis received nonsteroidal antiinflammatory drug therapy; 14 received additional therapy directed primarily to the cutaneous manifestations of psoriasis. Nine of these noted arthritis improvement with concurrent skin response; however, in 5 patients, arthritis activity increased, despite improvement of the cutaneous disease. Two other patients, treated with methotrexate, also had concurrent skin and joint improvement. These data suggest that psoriasis patients with HLA–DR + KTCs are at increased risk for the development of associated arthritis.

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Evidence of HLA-DR antigen biosynthesis by human keratinocytes in disease.

Cited by 162 publications

References 18 publications

Expression of HLA-DR molecules by keratinocytes, and presence of Langerhans cells in the dermal infiltrate of active psoriatic plaques.

Expression of HLA-DR molecules by keratinocytes, and presence of Langerhans cells in the dermal infiltrate of active psoriatic plaques.

Dendritic cells with antigen-presenting capability reside in airway epithelium, lung parenchyma, and visceral pleura.

Marked increase in the frequency of psoriatic arthritis in psoriasis patients with hla–dr+ keratinocytes

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