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

Abstract

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.

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

“…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).…”

“…Epidermal suction blisters from patients with psoriasis and from control subjects (see ref. 5) were generated at a temperature of 38°C and a negative pressure of 280 pounds per square inch. Single-cell suspensions of KTCs were obtained by trypsinization of suction blister roofs and contained < I % non-KTCs (16).…”

“…The findings were confirmed by radiographic studies (3). Criteria for severity of skin involvement have been described previously (5) and include the presence of more than 50% body coverage with psoriatic lesions, erythroderma, pustular psoriasis, or systemic signs (e.g., fever and fluid loss). Activity of PA was estimated by deterrnining the duration of morning stiffness, the number of painful or inflamed joints, and the need for nonsteroidal antiinflammatory drugs (NSAIDs) and analgesic drugs.…”

“…which is specific for Langerhans' cells (27), demonstrated HLA-DR molecules on OKT6-KTCs. The methodology used for these experiments has been described in detail previously (5). In selected patients, KTCs in suspension were tested with mouse MAbs by indirect immunofluorescence, using either a Leitz Ortholux 2 fluorescence microscope (28) (Leitz, Rockleigh, NJ) or an Ortho System 30H cell sorter (29) (Ortho Diagnostic Instruments, Westwood, MA).…”

“…Also, there is no reliable way to predict which patients with cutaneous psoriasis, a common disorder decting I-2% of North American whites, will develop associated arthritis. Accumulated evidence suggests that immunologic mechanisms play an important role in the pathogenesis of psoriasis (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15). We have reported previously that a proportion of psoriasis patients have HLA-DR+ keratinocytes (KTCs) in active plaques (5).…”