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K D Cooper

Publications and source records attributed to K D Cooper.

At least 145 records · Page 8Linked to original sources
PubMed1989

Expression and function of the UM4D4 antigen in human thymus.

UM4D4 is a newly identified T cell surface molecule, distinct from the Ag receptor and CD2, which is expressed on 25% of peripheral blood T cells, resting or activated. Monoclonal anti-UM4D4 is mitogenic for T cells and T cell clones. Since alternative activation pathways independent of Ag/MHC recognition may be important in thymic differentiation, the expression and function of UM4D4 was examined in human thymus. UM4D4 was found on the surface of 6% of thymocytes. All thymocyte subsets contained UM4D4+ cells but expression was greatest on thymocytes that were CD1- (12%), CD3+ (11%) and especially CD4-CD8- (18%). CD3+CD4- CD8- cells, most of which bear the gamma delta-receptor, were greater than or equal to 50% + for UM4D4. Moreover, anti-UM4D4 was comitogenic for thymocytes together with PMA or IL-2. Anti-UM4D4 also reacted strongly with a subset of thymic epithelial cells in both cortex and medulla. Dual color fluorescence microscopy, with anti-UM4D4 and antibodies to other thymic epithelial Ag, showed UM4D4 expression on neuroendocrine thymic epithelium but not on thymic fibrous stroma. Thus, UM4D4 is expressed on, and represents an activation pathway for, a subset of thymic T cells. In addition, this determinant, initially identified as a novel T cell activating molecule, is broadly expressed by neuroendocrine thymic epithelium. Although the function of UM4D4 on the thymic epithelial cells is not yet clear, it is possible that UM4D4 represents a pathway for the functional activation of a subset of the thymic epithelium as well as a subset of thymocytes, thus playing a dual role in T cell differentiation.

Antibodies, Monoclonal↗
PubMed1989

Rapid recovery of Langerhans cell alloreactivity, without induction of autoreactivity, after in vivo ultraviolet A, but not ultraviolet B exposure of human skin.

For therapeutic medical, cosmetic, and recreational reasons, humans expose themselves to increasing amounts of UVA. However, little is known of the photobiologic events associated with cutaneous carcinogenesis and photoaging that occur as a result of UVA exposure. UVB exposure of human skin abrogates the function of epidermal CD1+DR+ Langerhans cells and induces the appearance of CD1-DR+ non-Langerhans cell APC. This non-Langerhans cell APC population activates autoreactive immunoregulatory T cells that lead to suppressor-effector T cell function. In this report we show that, similarly to UBV, UVA exposure abrogates the function of CD1+DR+ Langerhans cells. However, in contrast to UVB, there is rapid recovery of Langerhans cell antigen-presenting cell activity and that CD1-DR+ non-Langerhans cell APC failed to appear to a significant degree. In keeping with the lack of CD1-DR+ epidermal cells, UVA exposed epidermal cells harvested 3 days after exposure functioned similarly to normal epidermis in that they activated alloreactive T cells but not autoreactive T cells in the absence of added Ag. This was in contrast to UVB irradiated epidermal cells that potently activate autoreactive T cells and contain CD1-DR+ cells. Thus, although both UVA and UVB initially depletes and inactivates CD1+DR+ Langerhans cells, the subsequent APC function of epidermal cells exposed to UVA differ profoundly from that of cells exposed to UVB. UVA radiation is less carcinogenic than UVB; differences in host responses to UV tumors may be linked to the rapid recovery of Langerhans cell function and the lack of induction of CD1-DR+ non-Langerhans cell APC after UVA exposure.

Adult↗
PubMed1989

Markedly diminished epidermal keratinocyte expression of intercellular adhesion molecule-1 (ICAM-1) in Sézary syndrome.

In mycosis fungoides the malignant T cells express lymphocyte function-associated antigen-1, which allows them to bind to epidermal keratinocytes expressing the gamma interferon-inducible intercellular adhesion molecule-1. In this report, a patient with leukemic-stage mycosis fungoides (Sézary syndrome) had widespread erythematous dermal infiltrates containing malignant T cells, but without any epidermotropism. We discovered that the T cells expressed normal amounts of functional lymphocyte function-associated antigen-1, but the keratinocytes did not express significant levels of intercellular adhesion molecule-1, which was probably due to the inability of the malignant T cells to produce gamma interferon. These results support the concept that the inability of malignant T cells to enter the epidermis may contribute to emergence of more clinically aggressive T-cell clones that are no longer confined to the skin, but infiltrate the blood, lymph nodes, and viscera, as is seen in Sézary syndrome.

Aged↗
PubMed1989

Lymphocytes and macrophages of the epidermis and dermis in lesional psoriatic skin, but not epidermal Langerhans cells, are depleted by treatment with cyclosporin A.

Since cyclosporin A (CsA) is an immunosuppressive agent, its beneficial effect in psoriasis suggests that immune cells may play a role in the pathogenesis and resolution of psoriasis. To determine early effects of CsA in psoriasis, we quantitated immune cells using double immunofluorescence microscopy on biopsy specimens obtained prior to therapy and after 3, 7, and 14 days of CsA therapy. CsA therapy resulted in significant reductions in the absolute number of immune cells (including T cells, monocytes/macrophages, and antigen presenting cells) contained within psoriatic skin. The effect was rapid, with over one-half of the reduction in the density of HLe1+ (human leukocyte antigen-1 positive or bone marrow derived) cells, including T cells, activated T cells, monocytes, and Langerhans cells (LCs), occurring within 3 days. Despite the overall reduction in the numbers of immunocytes in the skin, the proportion of T cells, Langerhans cells, and monocytes in relation to the total number of immune cells was unchanged with therapy, reflecting equally proportional losses of each subtype. Dermal CD1+DR+ cells (putative Langerhans cells), which are not found in normal skin but are present in lesional psoriasis skin, were virtually cleared from the papillary dermis after CsA therapy. Although absolute numbers of epidermal Langerhans cells, defined as cells expressing both CD1 (T6) and DR molecules (CD1+DR+), were also reduced after CsA, epidermal non-Langerhans CD1-DR+ cells (macrophages, activated T cells, DR- keratinocytes) demonstrated a proportionally greater decrease, with the ratio of CD1+DR+ Langerhans cells/non-Langerhans CD1-DR+ epidermal cells changing from a mean of 0.82 at baseline to 1.92 at day 14.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Cyclosporine in dermatology.

Cyclosporine is a potent immunosuppressive agent with no appreciable effect on the bone marrow and a selective inhibitory effect on helper T cells. Oral cyclosporine was first used to prevent organ rejection but also has been reported to be effective in other disorders. In cutaneous diseases that respond to oral cyclosporine helper T cells appear to be involved in their pathogenesis. This article reviews the cutaneous diseases that have been treated with cyclosporine and its pharmacology and side effects. Two significant adverse side effects are renal dysfunction and hypertension, both of which are reversible when short-term low-dose (less than 5 mg/kg per day) oral cyclosporine is discontinued. Lymphoma is unlikely in an otherwise healthy patient who has received low-dose oral cyclosporine for limited periods. The use of oral cyclosporine in any patient should be carefully considered in terms of the risk/benefit ratio and needs to be carried out under close medical supervision. In view of the limited experience with cyclosporine in dermatology, whenever possible its use should be confined to formal clinical studies with established protocols and guidelines. Further controlled studies need to be performed to evaluate the efficacy of low-dose cyclosporine in many dermatoses and its side-effect profile, particularly over the long term.

Animals↗
PubMed1989

Psoriatic epidermal cells demonstrate increased numbers and function of non-Langerhans antigen-presenting cells.

The recent findings that the immunosuppressant cyclosporine A (CsA) improves psoriasis raises the possibility that cellular immune processes play a major role in the pathogenesis of psoriasis. We therefore investigated the phenotype and function of cells within psoriatic epidermis that can play a role in cellular immunologic reactivity. Double fluorescence microscopic studies with monoclonal antibodies of epidermal cells in suspension (EC) and of histologic sections demonstrated that involved psoriatic skin contained a significantly increased number of non-Langerhans cell T6-DR+ EC (4.9 + 2.1%) relative to uninvolved (0.3 +/- 0.1%), p less than 0.01. This non-Langerhans cell population was comprised of DR+ monocytes, DR+ activated T lymphocytes, a few DR+RFD1+ antigen-presenting cells (APC), and DR+ keratinocytes. Langerhans cell (LC) levels in EC suspension were not different between involved and uninvolved psoriatic epidermis. Functional studies demonstrated that involved psoriatic epidermal cells had an increased capacity to induce T-cell activation and proliferation relative to uninvolved EC (p less than 0.04). This increased APC activity was due to the non-LC T6-DR+HLe1+ APC population and not to DR+ keratinocytes. These results demonstrate that involved psoriatic epidermal cells contain both an increased number and function of antigen-presenting cells. The pathogenetic mechanisms in psoriasis may be related to ongoing cellular immune responses in the skin, and the effect of CsA may be mediated through a suppressive effect on the enhanced antigen-presenting cell activity.

Antigen-Presenting Cells↗
PubMed1989

Decreased number and function of antigen-presenting cells in the skin following application of irritant agents: relevance for skin cancer?

The mechanism of irritant dermatitis and the immunologic consequences of such reactions are unclear. We evaluated the number and function of epidermal antigen-presenting cells contained in epidermal cell suspensions obtained from normal and irritant patch test reaction sites. Application of sodium lauryl sulfate or croton oil to human skin in vivo resulted in a progressive depletion in the number of epidermal OKT6+HLA-DR+ (T6+DR+) Langerhans cells (LC) from 3.1 +/- 0.2% of total epidermal cells (EC) to 1.2 +/- 0.1% after 8 d (mean values +/- SEM, N = 9). Between 1-4 d irritant patch test sites demonstrated an influx of non-Langerhans cell T6-DR+ cells. These cells were not DR+ keratinocytes but appeared to be of bone marrow derivation because they expressed the marker, HLe1. Among bone marrow derived cells, the T6-DR+EC appeared to be of monocyte, macrophage lineage, because they expressed the determinant recognized by the OKM5 (M5) antibody. Despite the induction of M5+DR+EC the total number of DR+EC showed progressively decreasing percentages over an 8-d period. Partial recovery to 73 +/- 12% of control value was observed at 2 weeks, with full recovery by 4 weeks after challenge. Concomitantly with the depletion of DR+EC, the capacity of EC to present alloantigens to T cells decreased. This reduction in antigen-presenting cell activity was strongly correlated to the reduction in total DR+ EC (r = 0.94, p less than 0.05). Thus, the capacity of irritants such as croton oil to abrogate the function of epidermal antigen-presenting cells may be related to the tumor promoting potential of these agents.

Administration, Cutaneous↗
PubMed1989

Characterization of factor XIIIa positive dermal dendritic cells in normal and inflamed skin.

The immunocytochemical identification and characterization of indigenous dermal dendritic cells (dermal dendrocytes) using a rabbit polyclonal antibody to clotting enzyme factor XIII subunit A (FXIIIa) was carried out on normal and inflamed human cutaneous tissue. The immunophenotype of FXIIIa positive dendritic cells was analysed with a panel of 18 monoclonal antibodies using immunoperoxidase and double immunofluorescence staining techniques. The antibody against FXIIIa detected highly dendritic dermal cells located particularly in the upper reticular and papillary dermis. Double fluorescence microscopy showed that FXIIIa positive cells were bone marrow derived (HLe-I+) and co-expressed monocyte, macrophage or antigen presenting cell markers (HLA-DR+, LFA-I+, HLA-DQ+, OKM5+, Mo I+, Mono-I+, Leu M3+). No labelling was obtained with cell markers for Langerhans cells (CDI), T lymphocytes (CD2), granulocytes (LeuMI) fibroblasts (Te7), intercellular adhesion molecule-I (ICAM-I) or endothelial cells (Factor VIII related antigen). Gamma interferon induced increased expression of HLA-DR and co-expression of ICAM-I on FXIIIa+ dermal dendritic cells in normal skin in organ culture. Moreover, in benign inflammatory dermatoses such as atopic eczema and psoriasis there was an increased number of FXIIIa+, DR+, ICAM-I+ cells in the upper dermis and foci of FXIIIa+ cells in the epidermis closely associated with lymphocytes. FXIIIa positive cells in human skin represent a specific population of bone-marrow dermal dendritic cells, distinct from Langerhans cells, that share some features common to mononuclear phagocytes (monocyte/macrophages). In addition, the detection of HLA-DQ on 48% of FXIIIa+ cells and the lack of OKMI in combination with high OKM5 expression suggests an antigen-presenting cell phenotype.

Adult↗
PubMed1989

Cyclosporine in lamellar ichthyosis.

In an open trial, five patients with lamellar ichthyosis showed no response to four weeks of treatment with oral cyclosporine (cyclosporine A) (6 mg/kg/d). Histologic examination of lamellar ichthyosis revealed hyperkeratosis; psoriasiform acanthosis; dilated, tortuous capillaries; and a slight perivascular lymphocytic infiltrate. Immunofluorescence studies revealed, in the epidermis, normal numbers of T6+DR+ Langerhans' cells and an absence of T cells and intercellular adhesion molecule-1 expression. In the papillary dermis, there were prominent capillaries as detected by staining with anti-factor VIII-related antigen. The endothelial cells also expressed large amounts of HLA-DR and intercellular adhesion molecule-1, suggesting that they were activated. Only occasional Langerhans' cells were found in the dermis. Histologic and immunofluorescence findings were unchanged with cyclosporine therapy. The effects of cyclosporine on lamellar ichthyosis are contrasted with those reported for psoriasis. Since lamellar ichthyosis and psoriasis share similar features of epidermal hyperproliferation and the presence of activated, dilated, tortuous vessels, but differ in the lack of immunologic cellular activity, their contrasting response to cyclosporine suggests that the target of the action of cyclosporine is the immune system rather than the keratinocyte or the endothelium. However, other factors may have to be considered.

Adult↗
PubMed1989

Epidermolysis bullosa acquisita in childhood. Differentiation from hereditary epidermolysis bullosa.

Epidermolysis bullosa acquisita (EBA), rarely reported in childhood, is described in a 10-year-old black girl. The age of onset during infancy and the clinical appearance mimicked hereditary dystrophic epidermolysis bullosa. Epidermolysis bullosa acquisita was diagnosed by direct immunofluorescence of perilesional skin, indirect immunofluorescence on normal epithelium and saline-split skin, direct immunoelectron microscopy, and immunoblotting of the patient's serum sample against partially purified EBA antigen/carboxyl domain of type VII collagen. Differentiation of mechanobullous disease in children is critical in that significant clinical benefit may be achieved in EBA with prednisone and/or dapsone therapy. A search for associated immunologic abnormalities and HLA-DR typing may help our understanding of EBA.

Age Factors↗
PubMed1989

Coexistence of pemphigus vulgaris and progressive localized scleroderma.

In this article, we describe a patient with progressive localized scleroderma, who subsequently developed pemphigus vulgaris on the previously affected sclerodermatous skin, and on the oral mucosa, the nasal mucosa, the laryngeal mucosa, and the scalp. The coexistence of pemphigus vulgaris with localized scleroderma and the histopathologic documentation of pemphigus vulgaris arising on a sclerodermatous skin have not been previously reported. Whether this is a random association or an association based on common immunologic pathomechanisms in pemphigus and localized scleroderma may be important in understanding these diseases.

Adult↗
PubMed1988

Human epidermal cells from ultraviolet light-exposed skin preferentially activate autoreactive CD4+2H4+ suppressor-inducer lymphocytes and CD8+ suppressor/cytotoxic lymphocytes.

In vivo exposure of human epidermis to UV abrogates the function of T6+DR+ Langerhans cells and induces the appearance of Ag-presenting T6-DR+ OKM5+ cells in the epidermis. Since UV exposure of murine skin results in Ts lymphocyte activation, we investigated the capacity of human epidermal cells (EC) harvested 3 days after in vivo UV exposure to activate regulatory and effector autologous T lymphocyte subsets. T lymphocytes were separated into CD8+ suppressor/cytotoxic lymphocytes and CD4+ helper/inducer lymphocytes by C lysis and panning. The CD4+ subset was further divided by using the 2H4 mAB to obtain CD4+2H4+ lymphocytes (inducers of TS lymphocytes) and CD4+2H4- lymphocytes (inducers of B cell Ig production and inducers of cytotoxic T cells). Unirradiated suction blister-derived EC from control skin (C-EC) and from skin exposed in vivo to UV (UV-EC) were cultured with purified autologous T lymphocyte subsets in the absence of added Ag. The resultant T lymphocyte proliferation was detected by [3H]thymidine uptake. UV-EC were highly effective in the stimulation of CD4+ lymphocytes, whereas C-EC were poor stimulators. The stimulator effect of UV-EC was abrogated after depletion of DR+ UV-EC. When CD4+ lymphocytes were fractionated, UV-EC consistently demonstrated enhanced ability to stimulate suppressor-inducer CD4+2H4+ lymphocytes relative to C-EC. Although less responsive than CD4+2H4+ lymphocytes, CD4+2H4- lymphocytes also demonstrated greater proliferation to UV-EC than to C-EC. Neither UV-EC nor C-EC were able to activate CD8+ lymphocytes devoid of CD4+ lymphocytes. However, after addition of rIL-2 at concentrations that allow binding only to the high affinity IL-2R on T lymphocytes, UV-EC induced vigorous proliferation of CD8+ lymphocytes, whereas C-EC induced only background levels of proliferation. C lysis of leukocytes resident within UV-EC resulted in 66 to 70% reduction of CD8+ lymphocyte proliferation. In conclusion, UV-EC may activate CD8+ lymphocytes by at least two pathways: (1) UV-EC activation of CD4+2H4+ lymphocytes may induce differentiation/proliferation of CD8+ suppressor cells and (2) UV-EC activation of CD4+ cells may induce IL-2 production, that, in combination with UV-induced epidermal leukocytes, stimulates CD8+ cells.

Adult↗
PubMed1988

Melanophages in inflammatory skin disease demonstrate the surface phenotype of OKM5+ antigen-presenting cells and activated macrophages.

Previous studies in our laboratory revealed that ultraviolet light induces the appearance of epidermal melanophages that have potent antigen-presenting ability, that can activate autoreactive T cells, and that exhibit the immunophenotype OKM5+, OKM1-, T6-, and DR+. Therefore we undertook immunophenotyping of melanophages in selected inflammatory mucocutaneous lesions to determine whether the OKM5+, OKM1- phenotype was limited to ultraviolet-induced inflammation or whether the occurrence of melanophages expressing this antigen-presenting cell phenotype was a more generalized phenomenon. Ten of the eleven patients with chronic inflammatory skin lesions demonstrated melanophages expressing the OKM5+, OKM1-, T6-, DR+ immunophenotype. In addition, they often expressed Mo3e, a marker of activated macrophages. In contrast, melanophages of a patient with post-inflammatory hyperpigmentation, although DR+, failed to express OKM5. These results are taken to support an active role for OKM5+, OKM1-, T6-, DR+ melanophages in inflammatory skin disease because these cells demonstrate the phenotype of activated inflammation-producing monocytes and potent antigen-presenting cells.

Antibodies, Monoclonal↗
PubMed1988

Expression of OKM5 antigen on epidermal cells in mycosis fungoides plaque stage.

To characterize and quantitate potential antigen-presenting cell subsets in the epidermis of patients with cutaneous T-cell lymphoma, epidermal cells in suspension were obtained from involved and uninvolved skin. Involved epidermis contained increased numbers of OKT6+HLA-DR+ Langerhans cells and a variable number of OKM5+ epidermal cells (ECs) in all mycosis fungoides (MF) patients tested (N = 14). The OKM5+ EC population from involved epidermis of MF patients were heterogeneous and comprised both OKM5+HLe1- keratinocytes and OKM5+HLe1+ leukocytes. Uninvolved epidermis, in 6 of 14 patients with MF, contained a small number of OKM5+ leukocytes; however, no OKM5+ keratinocytes were detected. Neither OKM5+ leukocytes nor OKM5+ keratinocytes were detected in the epidermis obtained from healthy controls. The increased number of potential antigen-presenting cells, that is, OKT6+HLA-DR+ Langerhans cells and OKM5+HLA-DR+ monocytic leukocytes, in the epidermis of patients with MF may be important for the activation of abnormal T cells contained within the epidermis of these patients. Such activated T cells may release gamma-interferon and induce expression of both HLA-DR and OKM5 antigens on keratinocytes. OKM5+ keratinocytes are present in the epidermis of patients with MF, but not in normal skin, and may thus play a role in the pathogenetic mechanisms of mycosis fungoides by recruitment of immunocompetent cells to the epidermis.

Aged↗
PubMed1988

Rapid occurrence of nodular cutaneous T-lymphocyte infiltrates with cyclosporine therapy.

Cyclosporine, a potent immunosuppressive agent, has been successfully used in the treatment of several dermatologic conditions including psoriasis. However, the drug does have an array of toxic side effects that need to be carefully considered when determining the risk-benefit ratio for the treatment of skin disease. We present another potential adverse effect of cyclosporine, namely, a benign lymphocytic infiltrate. This eruption developed in a patient with psoriasis after only ten days of cyclosporine therapy. The exact mechanism by which cyclosporine induced the lymphocytic infiltrate is unknown, but it is postulated that cyclosporine caused an imbalance of T-cell regulatory systems, thus resulting in an expanded T-cell subpopulation and the clinical manifestation of erythematous papules and nodules.

Biopsy↗