Ia-like antigens in lichen planus

The occurrence of Ia-like antigens in the skin of patients with lichen planus was studied by an indirect immunofluorescence (IIF) technique with use of immunosorbent-purified anti-Ia antibodies. Normal skin from the patients and skin from healthy persons showed dermal histiocytes and epidermal suprabasal dendritic cells expressing these antigens. In lichen planus lesions Ia-like antigens were found on virtually all mononuclear cells in the dermal infiltrate and showed an intercellular pattern in the epidermis. The finding of cells expressing Ia-like antigens in the dermal infiltrate, most probably activated T lymphocytes, renders likely a cell-mediated type of reaction in the pathogenesis of lichen planus.     

Immunopathology of cutaneous human lupus erythematosus defined by murine monoclonal antibodies

Skin biopsy specimens obtained from involved skin from sixteen patients with systemic and discoid lupus erythematosus were studied. Murine monoclonal antibodies with a biotin-avidin-horseradish peroxidase staining system were used. The findings consisted of a marked reduction in the number of epidermal Langerhans cells defined by surface antigens, reduced HLA-DR (Ia-like) antigens on the surface of dermal capillary endothelium, and mononuclear cell infiltrates characterized by a predominance of helper T lymphocytes and an increase in the number of mononuclear phagocytic cells. B lymphocytes were rarely identified. The number of T lymphocytes within the dermis correlated inversely with both the number of HLA-DR-positive epidermal Langerhans cells (p less than 0.01) and the HLA-DR staining of dermal capillary endothelium (p less than 0.01). These findings suggest that a T lymphocyte-mediated immune response associated with a reduction in Langerhans cells and capillary endothelium HLA-DR antigens is involved in the inflammatory process of lupus erythematosus skin.     

Fibronectin in leprosy lesions: observations using monoclonal antibodies to human fibronectin

Croystat sections of dermal lesions from 33 untreated patients with leprosy were studied by indirect immunofluorescence using monoclonal antibodies to human fibronectin. Macrophages in borderline (BL) and lepromatous (LL) leprosy showed intense staining with antifibronectin antibodies. In the tuberculoid lesions cells of the mononuclear phagocyte series in an epithelioid cell granuloma stained for fibronectin. The lymphocytes surrounding these granulomas also showed the presence of fibronectin. These results suggest that the granuloma of leprosy consists of macrophages expressing fibronectin and the lymphocytes in the lesion also appear to express this protein. In six borderline cases, the sub epidermal collagen band showed intense staining with antifibronectin antibodies. In addition, the distribution of Ia-like antigens and fibronectin was studied on the plastic adherent cells obtained from peripheral blood of 11 untreated patients with leprosy. Results indicate that higher percentage of adherent cells from lepromatous patients express fibronectin in comparison to adherent cells from tuberculoid patients or controls. However, no difference was observed in the expression of the Ia-like antigens by the adherent cells, from these patients.     

T6 positive cells in the peripheral blood of burn patients: are they Langerhans cells precursors?

Peripheral blood mononuclear cells of 14 patients suffering thermal injury were separated by affinity chromatography on peanut agglutinin (PNA) coupled to Sepharose macrobeads. The resulting PNA positive subset was 14% of the total mononuclear population. About 30% of these cells were found to coexpress T6(CD1), Ia-like and the myeloid differentiation antigens My4(CDw14) and Mo1(CD11). In comparison, the PNA+ subset from normal blood donors (about 5% of total mononuclear cells) contained mature monocytes that were found to be T6 negative. Electron microscopic studies using immunogold labeling showed that the T6 positive cells were slightly smaller than monocytes but larger than the classical lymphocytes and had common morphologic features with the Langerhans cells of the skin. Considering that patients suffering extensive damage of the epidermis require fast renewal of all skin elements, it is possible that the cells we identified in their peripheral blood are the precursors of the Langerhans cells of the skin en route from bone marrow to the epidermis.     

T-cell infiltrate in Lichen Planus. Demonstration of activated lymphocytes using monoclonal antibodies

Double layer immunocytochemical procedures were performed on fresh frozen serial sections of lichen planus (LP), using three monoclonal antibodies: OKT3 (T-cells) and two anti Ia-like antigens, monoclonal antibodies. Lymphocytes in dermal LP infiltrates were OKT3 positive and Ia-like positive; lymphocytes in the paracortical area of human normal lymph-node were OKT3 positive and Ia-like negative. Unstimulated peripheral blood-OKT3 positive, E-rosette forming cells of normal donors were Ia-like negative, while the same T-cells, when mitogen-stimulated, became Ia-like positive. Therefore, in dermal infiltrates of LP, T-lymphocytes are Ia-like positive cells, representing an antigen-stimulated T-cell population. The in situ presence of activated T-lymphocytes seems to support the hypothesis of an immunological nature of LP.     

Perforin expression in peripheral blood lymphocytes and skin-infiltrating cells in patients with lichen planus

BACKGROUND: Current evidence suggests that lichen planus is a T-cell-mediated autoimmune disease in which cytotoxic mechanisms have been poorly investigated. OBJECTIVES: We investigated the expression of perforin in subpopulations of peripheral blood lymphocytes (PBL) in exacerbation and remission phases of the disease as well as in skin lesions. METHODS: We performed a simultaneous detection of perforin (intracellular molecule) and cell surface antigens on PBL by flow cytometry, and skin lesions were investigated by immunohistochemistry. RESULTS: The most interesting finding was a significant increase of perforin expression in cytotoxic T lymphocytes (CD3+ perforin+ cells) in the exacerbation phase of disease (P < 0.05), which was mostly located in the CD8+ subpopulation (CD8+ perforin+) (P < 0.01). Using immunohistochemistry we confirmed the infiltration of T lymphocytes in skin lesions, especially of CD4+ and CD8+ phenotypes, compared with uninvolved (P < 0.05) and healthy skin (P < 0.01). The expression of perforin was also significantly higher in lesional skin compared with nonlesional and healthy skin (P < 0.05). CONCLUSIONS: Our results clearly show the upregulation of perforin expression in peripheral blood as well as in lesions of patients with lichen planus and therefore suggest an important role for perforin in this autoimmune disease.     

Human Ia-like-antigen-expressed cutaneous T cell lymphoma associated with Epstein-Barr virus infection

2 cases of cutaneous T cell lymphoma are reported. In both cases immunological studies revealed that the tumor cells from the cutaneous lesions had human Ia-like antigen on the cell surface, which was considered to be alloantigen primarily present on B lymphocytes. Serum examination showed an extremely high titer of two types of antibody against Epstein-Barr (EB) virus in the 1st case and a relatively high titer of one type of antibody in the 2nd case, suggesting that the patients had EB virus infection. Recently, some hematologists found the significant correlation of T lymphocytosis and the appearance of human Ia-like antigen in infectious mononucleosis. Based on these findings, it is assumed that EB virus has the ability of the immunological transformation of cutaneous neoplastic lymphocytes, and so we should not overlook the susceptibility of phenotypical changes of the original cell by EB virus when the immunological classification of cutaneous malignant lymphoma is done.     

CD103+T细胞在银屑病皮损中的表达

目的：明确银屑病患者皮肤CD103+T细胞的表达及其与银屑病严重程度的关系。方法：免疫组化检测29例银屑病患者皮损和非皮损皮肤及6名健康对照皮肤中表皮及真皮CD103+T细胞的表达。计算银屑病患者PASI值。结果：CD103+T细胞主要在真皮表达。银屑病患者皮损和非皮损真皮中每个高倍视野CD103+T细胞百分率分别为（26.06%±11.72）%和（12.82±4.5）%（P<0.05）;健康人对照皮肤真皮内CD103+T细胞百分率为（7.47±1.3）%,明显低于银屑病非皮损区（P<0.05）。银屑病患者皮损中,CD103+T的表达与PASI值正相关（P<0.05）。 结论：真皮中CD103+T细胞可能与银屑病的发病及严重程度有关。     

Pathogenetic mechanisms of vitiligo in a patient with Sézary syndrome

Patients exhibiting association between vitiligo and cutaneous T-cell lymphoma (CTCL) remain rare and it is not known whether some T-cell subpopulations of CTCL in the skin are able to recognize specific melanocytic epitopes and thus induce vitiligo. The aim of our study was to determine whether T cells specific to melanocyte differentiation antigens were detectable among tumour-infiltrating lymphocytes (TIL) in the hypopigmented skin of a patient with Sézary syndrome (SS). A 71-year-old patient presented with SS and developed vitiligo during the course of her disease. Immunohistochemical studies showed staining with HMB45 and MelanA antibodies in the pigmented skin biopsy, whereas no staining was observed in the hypopigmented skin biopsy. To analyse responses to melanocyte differentiation antigens, we used a transient COS transfection assay that permits an estimation of CD8 T-cell responses against a large number of HLA/antigen combinations. This technique allowed the detection of melanocyte differentiation antigen-specific T lymphocytes, directed mainly against Melan-A/MART1 antigen in the HLA-A*23 context. Our study supports the concept that vitiligo that has developed during the evolution of a CTCL is related to the presence of a T-lymphocyte subpopulation reactive against melanocyte differentiation antigens (mainly Melan-A/MART1) present in skin lesions. The role of interferon in the induction of this T-lymphocyte subpopulation is discussed.     

Differentiation of human T lymphocytes: II. Phenotypic difference in skin and blood malignant T-cells in cutaneous T-cell lymphoma

The cell surface antigen phenotype of circulating and skin malignant T-cells in patients with cutaneous T-cell lymphoma were studied. The mature T-cell antigen phenotype of the malignant T-cells was identical for circulating and skin malignant T-cells. In contrast, skin malignant T-cells expressed the immature human T-cell antigen Thy-1, surface membrane transferrin receptors, and Ia-like determinants while circulating malignant T-cells did not express these antigens. Skin infiltrating T-cells in benign dermatoses also expressed Thy-1 and Ia-like determinants. These observations support the notion that the skin is a major site of extrathymic T-cell differentiation and may promote phenotypic changes in circulating T-cells that home to skin.     

皮肤淀粉样变性皮损中T/B细胞的检测

目的 探讨原发性皮肤淀粉样变性皮损中T/B细胞变化的差异及其意义.方法 60例患者局部病变皮损标本、29例正常人皮肤标本,分别进行CD3、CD4、CD8、CD20免疫组化染色.结果 与正常人对照组比较,皮肤淀粉样变性皮损中,淋巴细胞总数、CD3⁺T细胞、CD8⁺T细胞的均数增高(P<0.05),CD4⁺T细胞均数无明显增高(P>0.05),CD4⁺/CD8⁺T细胞比值下降(P<0.05),CD20⁺B细胞均数增高(P<0.05).T淋巴细胞、B淋巴细胞在原发性皮肤淀粉样变性苔藓样、斑疹型或双相型三种分型病变间相互比较,差异无统计学意义(P>0.05).结论 原发性皮肤淀粉样变性局部皮损存在有T/B淋巴细胞的异常表达,但三种病变类型间病变机制的免疫学异常无区别.     

Distribution of interleukin-2 receptor bearing lymphocytes in the skin. A comparative study of allergic and irritant contact dermatitis, tuberculin reaction and cutaneous T cell lymphoma

The tissue distribution of T cells and interleukin-2 receptor bearing (Tac+) lymphocytes was studied immunohistochemically in frozen sections of biopsies from inflamed skin. In skin lesions caused by irritant or immunologic stimuli, relatively few (less than 5%) of the total dermal infiltrating T cells were Tac+, but in both types of conditions the Tac+ cells showed a predeliction for the epidermis. In skin lesions from patients with cutaneous T cell lymphoma a relatively high proportion of dermal T lymphocytes were Tac+. Tac+ as well as Tac- T lymphocytes may thus migrate to a tissue secondary to several different stimuli. The demonstration of a non-random distribution of Tac+ lymphocytes in the non-malignant inflammatory conditions in the present study indicate that the epidermis may have a special role in the activation of T lymphocytes.     

Mononuclear cell patterns in the skin. An immunohistological and morphometrical analysis

A large variety of skin diseases is characterized by the presence of mononuclear cell infiltrates in the dermis and to some extent in the epidermis. We have investigated frozen material of 566 lesions of benign and malignant skin diseases by immunohistological methods with a panel of 20 monoclonal antibodies; quantitative studies using computer-assisted image analysis were additionally performed in 80 specimens. In all reactive lesions, mononuclear cells were arranged in distinct compartments simulating the architecture of normal lymphatic tissue. A qualitatively uniform T cell compartment (mainly helper-inducer T lymphocytes, suppressor-cytotoxic T lymphocytes, Langerhans' cells) with slight quantitative differences was found in all inflammatory skin diseases, in peritumoral infiltrates, and also in normal skin. The B cell compartment (B lymphocytes, few T lymphocytes and monocytes) is only rarely seen (some B cell lymphomas and pseudolymphomas). The monocyte compartment (monocytes, few T lymphocytes) associated with a T cell compartment is typical for granulomatous skin lesions. The epidermis forms a separate functional region, which might evolve into a lymphoepithelial compartment in diseased skin. Low-grade malignant lymphomas of the skin display similar architectural patterns as reactive lesions, whereas high-grade malignant lymphomas do not. Obviously the mononuclear cells in the skin are usually arranged in compartments and form a limited number of distinct patterns. As similar patterns are found in diseases that are completely different with respect to clinical appearance, histological features, cause, and outcome, the patterns are not disease specific but reflect general anatomical-functional relationships of inflammatory cells and the skin.     

自然杀伤T细胞在银屑病发病中的研究进展

自然杀伤T细胞是一种兼具自然杀伤细胞和T细胞特性的独特淋巴细胞群,可同时表达T细胞和自然杀伤细胞表面标记.自然杀伤T细胞可识别由CD1d分子提呈的抗原,快速分泌大量细胞因子,并可调控T细胞的分化,在自身免疫性疾病中发挥重要的调节作用.基于目前对于银屑病病理过程的研究,发现寻常性银屑病皮损处淋巴细胞、单核细胞浸润明显,尤其是T淋巴细胞和树突细胞在表皮或真皮浸润为银屑病的重要病理特征,表明免疫系统参与该病的发生和发展.目前认为,银屑病是遗传和环境等多种因素相互作用的多基因遗传性炎症性皮肤病,发病机制与免疫介导有关.     

Scarring skin lesions of discoid lupus erythematosus are characterized by high numbers of skin-homing cytotoxic lymphocytes associated with strong expression of the type I interferon-induced protein MxA

BACKGROUND: Infiltrating T lymphocytes are considered to play a major pathological role in skin lesions of cutaneous lupus erythematosus (CLE), a cutaneous autoimmune disease of unknown aetiology. Earlier histological studies revealed that the inflammatory infiltrate in CLE skin lesions is predominantly composed of T lymphocytes, with a slight predominance of CD4+ over CD8+ T cells, but failed to explain the development of scarring skin lesions, characteristic for chronic discoid lupus erythematosus (CDLE). Because recent investigations have highlighted the relevance of cytotoxic lymphocytes in autoimmune tissue destruction, we hypothesized that the scarring CDLE lesions might be caused by cytotoxic T lymphocytes. OBJECTIVES: To analyse skin biopsies of 15 patients with CLE [10 female, five male; localized CDLE (lCDLE), n = 5; disseminated CDLE (dCDLE), n = 5, subacute CLE (SCLE), n = 5] and five control biopsies taken from healthy controls and to characterize the inflammatory infiltrate. Methods We used immunohistochemistry, including staining for the cytotoxic molecule granzyme B, the skin-homing molecule cutaneous lymphocyte antigen (CLA) and the protein MxA, which is specifically induced by type I interferons (IFNs). RESULTS: We found a strong coexpression of granzyme B and CLA on lesional lymphocytes of patients with scarring lCDLE and dCDLE, which was significantly enhanced when compared with nonscarring SCLE and healthy controls. The increased expression of granzyme B was closely associated with the lesional expression of the type I IFN-induced protein MxA. CONCLUSIONS: Our results provide evidence that type I IFNs and potentially autoreactive cytotoxic lymphocytes targeting adnexal structures are highly associated with scarring lupus erythematosus lesions and might be responsible for their scarring character.     

寻常型银屑病皮肤中皮肤归巢T细胞免疫组化研究

目的 探讨皮肤归巢T细胞在寻常型银屑病(PV)发病中的作用。方法 采用间接免疫荧光双标法研究正常人皮肤和PV患者皮肤中浸润的皮肤归巢T细胞分类及其变化。结果 ①正常人皮肤及PV皮损中浸润的T细胞绝大多数表达皮肤淋巴细胞相关抗原(CLA),CLA⁺细胞高度表达CD45RO,只有个别为CD45RO阴性。②进行期皮损CD4⁺CLA⁺及CD8⁺CLA⁺T细胞数高于静止期皮损(P<0.05),静止期皮损CD4⁺CLA⁺细胞数高于消退期皮损(P<0.05),消退期皮损CD8+CLA+细胞数高于PV外观正常皮肤(P<0.05),进行期皮损周边外观正常皮肤CD4⁺CLA⁺及CD8⁺CLA⁺细胞数高于静止期皮损周边外观正常皮肤(P<0.05).③部分病例皮损的表皮中见大量CLA⁺树突状细胞,正常人皮肤未见此细胞。结论 正常人皮肤及PV皮损中T细胞绝大多数为皮肤归巢T细胞;进行期及静止期PV皮损中浸润的细胞主要为CD3⁺、CD4⁺、CD45RO⁺、CLA⁺T细胞,CD3⁺、CD4⁺、CD45RO⁺、CLA⁺T细胞可能在PV发病中起重要作用。     

Expression of a cell adhesion protein (VLA β) in normal and diseased skin

Biopsies from normal skin (n = 17) and various cutaneous disorders (n = 83) were examined immunohistologically for reactivity with an antibody (CD29) against the common beta chain of the VLA integrin family. In normal skin, CD29 recognized a number of cell types, i.e. endothelial cells, fibroblasts, T lymphocytes and basal keratinocytes. Similar cells were positive in diseased skin, but the expression of VLA beta was upregulated on keratinocytes. The phenotype of the VLA beta-positive T cells was examined in more detail by staining with anti-T-cell antibodies, i.e. CD3, CD4, CD8, CD45RO (UCHL1) and CD45R (2H4). These studies showed that most of the T cells in normal skin, benign cutaneous conditions and early cutaneous T-cell lymphomas (CTCL) expressed a similar phenotype and resembled antigen committed 'memory' (helper/inducer) cells (CD4+, CD29+, CD45RO+, CD45R-). In advanced CTCL, expression of these antigens was more variable, and many of these infiltrates showed aberrant (or unusual) expression of CD29, CD45RO, CD45R and other T-cell antigens. It is concluded that several cells involved in cutaneous immune reactions express a molecule (VLA beta) which acts as a receptor for extracellular matrix components. This molecule is important for the attachment of cells to connective tissue constituents and may act to facilitate the migration of lymphocytes (and other cells) during immune reactions in normal and diseased cutaneous conditions. Advanced CTCL differ from the early lesions and it is possible that there is a progressive accumulation of increasingly malignant (or transformed) cells in these conditions.     

Analysis of major histocompatibility antigens and the mononuclear cell infiltrate in halo nevi

A series of monoclonal antibodies was used to characterize the nevomelanocytes and the inflammatory infiltrate of 11 halo nevi in different stages of resolution, employing an immunoperoxidase technique. Three of the 11 halo nevi histologically showed signs of mild or moderate nevomelanocytic atypia. It was found that the vast majority of the nevomelanocytes in halo nevi with a dense inflammatory infiltrate markedly expressed HLA-A,B,C antigens, while expression was not demonstrable in nevocellular nests not adjacent to the mononuclear infiltrate. No difference in expression of HLA-A,B,C antigens was found between the 3 cases with mild or moderate nevomelanocytic atypia and the other cases lacking atypia. Expression of HLA-DR (Ia-like) antigens was found on few nevomelanocytes in only 2 of 11 lesions. The cellular composition of the mononuclear inflammatory infiltrate showed a predominance of T cells (80% or more) with a relatively high proportion of cytotoxic/suppressor T cells. Most of the T cells showed signs of activation as judged by staining for HLA-DR antigens. These results demonstrate that the expression of HLA-A,B,C antigens on the nevomelanocytes and the cellular composition of the mononuclear inflammatory infiltrate in halo nevi are very similar to that in malignant melanomas and dysplastic neiv. These findings also indicate the expression of HLA-A,B,C antigens on nevomelanocytes is primarily dependent on the presence of T-cell immune response and not necessarily related to the presence of nevomelanocytic atypia.