Immunoglobulins and Their Receptors on Epidermal Langerhans Cells in Atopic Dermatitis

To elucidate the etiological role of immunoglobulin molecules on Langerhans cells (LCs) in atopic dermatitis, we conducted immunohistochemical studies on the localization of immunoglobulin G1 (IgG1), IgG2, IgG3, IgG4, IgA and IgM on epidermal LCs from 30 patients with atopic dermatitis (AD) and five non-atopic healthy volunteers. We also investigated the types of receptors for the immunoglobulins (FcεRI, FcεRII, FcγRI, FcγRII, and FcγRIII) on epidermal LCs in the patients. IgE positive epidermal LCs were observed in 28 of 30 AD patients, and 46.7% of the epidermal LCs were positive for IgE. Both IgG1- and IgG2-positive epidermal LCs were obserbed in 70% of AD patients, and 21.8% and 28.7% of the total epidermal LCs were positive for IgG1 and IgG2, respectively. IgG3- or IgG4-positive LCs were present in only small proportions of AD patients. IgA-positive LCs were observed in 8 AD patients; our study suggested that the IgA bound on LCs was secretory IgA (S-IgA). These surface immunoglobulins were observed significantly more frequently on epidermal LCs in the involved skin of AD than in clinically uninvolved skin. No IgM-positive epidermal LCs were observed in the AD patients or healthy volunteers. In non-atopic healthy controls, no immunoglobulin-binding LCs were observed. In receptors for immunoglobulins, FcεRI and FcγRII were exclusively expressed on nearly all epidermal LCs from all AD patients and all non-atopic controls. These results suggested that not only IgE but also IgG and IgA may play some etiological role in the pathogenesis of AD.     

高亲和力IgE-he受体介导IgE合至郎格罕细胞

正常人表皮郎格罕细胞(LC)能特异性结合IgiJ,这种结合能被针对高亲和力IgE-Fc受体(FcERI)单克隆抗体(mAb)15-1完全阻断.然而,抗低亲和力IgE-Fc受体(FcsRII)mAb MHM、抗II型IgG-Fc受体(FcγRII)mAb IV3或乳精则不能阻断IgE结合至LC.这些观察结果提示IgE结合至LC是通过FcεRI,而不是FceRII,FcyRII或IgE结合蛋白(eBP)所介导.免疫标记研究进一步显示抗FcεRI mAb能特异性标记LC表面本研究首次证明表皮LC具有FcεRI.     

特应性皮炎患者IgE受体FcεRIα基因多态性研究

目的 探讨FcεRIα基因序列研究基因多态性与特应性皮炎的相关性.方法 提取特应性皮炎患者(97例)和正常人(283例)基因组DNA并进行扩增,通过高温连接酶检测法(PCR-LDR)测定FcεRIα基因远端启动子的序列,检测其SNP位点,并用SPSS软件进行统计处理.结果 ①FcεRIα基因启动子区rs61828219位点存在G＞T多态性,rs12135235位点为TT纯合子,rs36233780位点为AA纯合子.②特应性皮炎患者组和正常人对照组间的rs61828219位点基因突变频率分别为1.04%和2.17%,两组间差异无统计学意义(P＞0.05).结论 汉族人FcεRIα基因rs61828219位点存在G＞T基因多态性,与特应性皮炎相关性不显著,s12135235位点和rs36233780位点不存在多态性.     

Enhanced expression of the high-affinity receptor for IgE (Fc(epsilon)RI) associated with decreased numbers of Langerhans cells in the lesional epidermis of atopic dermatitis

Epidermal Langerhans cells (LCs) and the high-affinity receptor for IgE (Fc(epsilon)RI) on their surface are considered important in the pathogenesis of atopic dermatitis (AD). We investigated the numbers of epidermal LCs and their Fc(epsilon)RI expression in patients with AD and healthy controls. Biopsy specimens taken from lesional skin from 17 patients with AD, non-lesional skin from five patients with AD and normal skin from five healthy individuals were immunohistochemically stained with a monoclonal antibody against CD1a or with either of two monoclonal antibodies against two different epitopes of Fc(epsilon)RI alpha chain. Many dendritic cells were positively stained with anti-CD1a antibody in the epidermis of each skin sample, and fewer cells were stained with anti-Fc(epsilon)RI antibodies. The numbers of epidermal LCs positive for Fc(epsilon)RI were significantly increased in both lesional and non-lesional skin from AD patients compared with those in normal skin, suggesting important roles of Fc(epsilon)RI+LCs in the pathogenesis of the disease. In contrast, the numbers of total epidermal LCs (CD1a-positive) were decreased in AD lesional skin compared with those in non-lesional skin from AD patients and in normal skin from healthy subjects. Together with our finding that the numbers of epidermal LCs were negatively correlated with the clinical severity of the AD lesions, we concluded that epidermal LCs may decrease in some conditions of AD, probably in lesions with severe inflammation.     

In situ expression of the costimulatory molecules CD80 and CD86 on Langerhans cells and inflammatory dendritic epidermal cells (IDEC) in atopic dermatitis

Abstract The functional expression of costimulatory molecules on antigen-presenting cells may be a key event in the pathogenesis of atopic dermatitis (AD). Recently, the expression of CD86 (B7-2/B70) has been demonstrated on CD1a⁺ epidermal dendritic cells (DC) in AD lesions by immunohistological and functional analysis. Therefore, we sought to further characterize the in situ expression of costimulatory molecules on these cells, considering the two subpopulations of (1) CD1a⁺⁺⁺/CD11b^– Langerhans cells (LC) containing Birbeck granules and (2) CD1a⁺/CD11b⁺⁺⁺ inflammatory dendritic epidermal cells (IDEC), devoid of Birbeck granules, from AD and other inflammatory skin diseases. Flow cytometry, skin mixed lymphocyte reactions (SMLR) and immunohistological analysis were performed, and showed that IDEC and not LC are the relevant cells expressing the costimulatory molecules CD80 and CD86 in situ. This expression varied with the underlying diagnosis, with AD showing the highest expression of both CD80 and CD86 in situ. Furthermore, the expression of CD80, CD86 and CD36 were significantly correlated. With short-term culture, both CD80 and CD86 were further upregulated on LC and IDEC. Finally, anti-CD86 antibody reduced the stimulatory activity of epidermal DC. These results indicate that costimulatory molecules on LC and IDEC might play a role in the pathogenesis of AD. Received: 7 June 2000 / Accepted: 21 January 2001     

Vitamin D modulates the allergic phenotype of dendritic cells in children with atopic dermatitis

Vitamin D (VD) deficiency has been associated with increased incidence and severity of atopic dermatitis (AD), but the mechanisms through which VD may ameliorate AD are unclear. We compared the phenotypic characteristics of circulating myeloid and plasmacytoid dendritic cells (mDCs and pDCs, respectively) of children with AD vs healthy controls (HC) and evaluated if VD can modulate the allergic phenotype of circulating DCs in AD patients. Although there was no difference in frequency of circulating DCs between groups, among children with AD there was an inverse correlation between SCORAD and circulating total DCs and mDCs. In AD, serum IgE concentration correlated with FcεRI and surface‐bound IgE expression on mDCs and pDCs; pDCs expressing FcεRI and IgE were significantly increased compared to HC. Ex vivo, 1,25(OH)₂D₃ significantly decreased FcεRI expression on mDCs and surface‐bound IgE on mDCs and pDCs. Oral VD supplementation reduced expression of surface‐bound IgE on pDCs in children with AD. In summary, VD decreases the allergic phenotype of circulating DCs in children with AD, a potential mechanism for how VD supplementation may improve AD severity. Future studies are needed to further assess the role of VD supplementation as an immunomodulatory therapy for AD.     

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

Summary Since cyclosporin A (CsA) is an immuno-suppressive 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. Thus, early in the course of therapy, CsA appears to be effective at clearing CD1^-DR⁺ cells while leaving LC relatively intact in the epidermis.This work was supported in part by the Babcock Foundation     

IgE receptors in Langerhans cells. A link between the environment and the immune system?]

The demonstration of IgE-bearing epidermal Langerhans cells (LC) opened up new perspectives in the pathophysiology of atopic eczema. IgE receptors on LC have now been identified and characterized: all three IgE-binding structures so far known to be present in the human immune system have been demonstrated on LC, i.e. the low-affinity receptor for IgE (Fc epsilon RII/CD23), the so-called IgE-binding protein (epsilon BP) and the high-affinity receptor for IgE (Fc epsilon RI), which had hitherto been considered to be expressed exclusively on mast cells and basophils. Functionally, there is some evidence that these structures may be involved in the release of cytokines and/or IgE-mediated antigen focusing. Considering the specificity of IgE for environmental allergens and the particular place of LC in primary and secondary immune responses, it can be speculated that LC in the skin and mucosae play a major role in mechanisms of sensitization to such allergens and in the genesis of IgE-mediated diseases. Finally, IgE receptors on LC may provide targets for new therapeutic approaches in atopic diathesis.     

Adhesion molecules in lesions of American cutaneous leishmaniasis

Abstract Accessory signals, which include adhesion molecules, MHC-II molecules and cytokines. are necessary to foster the interaction between memory T cells and epidermal cells, that is required to promote cutaneous inflammatory responses. American cutaneous leishmaniasis (ACL) is characterized by a spectrum of immunological manifestations, and is a prototype disease for the study of regulatory mechanisms involved in immune protection against protozoal infection. In the present study, we show that diffuse cutaneous leishmaniasis (DCL) epidermis contains keratinocytes that do not express ICAM-I and HLA-DR molecules. Langerhans cells (LC) are within normal values or somewhat lower, and a very few cells expressing the HB15 molecule a new described member of the Ig superfamily are found in such lesions. Mucocutaneous leishmaniasis (MCL) epithelium shows an increased expression of ICAM-1 and HLA-DR molecules, few HBI5⁺ cells, and an absence of epithelial LC. Localized cutaneous leishmaniasis (LCL) epidermis displays ICAM-⁺ keratinocytes organized in patches, a uniform expression of HLA-DR, hyper-plasia of LC, and numerous HBI5⁺ cells. In all forms of the disease, infiltrating T cells express more LFA-1β than LFA-1α, but LFA-1β⁺ cells are more abundant in LCL granulomas. In contrast, there are more LFA-lα⁺ cells in DCL and MCL than in LCL granulomas. LCL lesions also show the highest numbers of HB15⁺ cells within the granu-loma. These results indicate the importance of adhesion molecules in ACL lesions, and open new possibilities for therapeutic schemes oriented towards the control of cell migration.     

Lymphocyte trafficking in psoriasis: a new perspective emphasizing the dermal dendrocyte with active dermal recruitment mediated via endothelial cells followed by intra-epidermal T-cell activation

Prominent within the inflammatory infiltrate of psoriasis are HLA-DR positive T lymphocytes and factor XIIIa positive dermal dendrocytes. Many investigators studying psoriasis have assumed that the HLA-DR positive T cells are activated, and thereby capable of producing lymphokines such as gamma interferon. However, by immunohistochemical analysis, greater than 95% of the dermal T cells in psoriatic lesions are Ki-67 negative, which suggests that they are in a resting or non-cycling (Go) state. In contrast to the dermal T-cell population, the epidermal T-cell population contains a greater population of Ki-67 positive lymphocytes. The entry of the T cells into the epidermis is, therefore, apparently associated with an important activation event, which in all likelihood involves interaction with the keratinocyte. The presence of activated intraepidermal T cells has been substantiated by the ability to detect gamma interferon mRNA by polymerase chain reaction in epidermal sheets of psoriatic lesions. The pathophysiologic implication in psoriasis for these distinctions and compartmentalization involving dermal and epidermal T cells are placed into the context of a cascade of cellular trafficking events, which are further dissected into a specific network of molecular mediators of inflammation. This report suggests that more attention should be placed on the microenvironment of the skin, with specific emphasis on the mechanism by which T cells accumulate in the dermis and epidermis, and elucidation of the selective inductive and recruitment capabilities of endothelial cells, perivascular dermal dendrocytes, and keratinocytes.     

Internalization and acidification of surface HLA-DR molecules by epidermal Langerhans cells: a paradigm for antigen processing

CD4+ T lymphocytes recognize multi-molecular complexes, formed by major histocompatibility complex class II molecules and exogenous antigens, on the surface of antigen-presenting cells (APC). For most protein antigens, processing is required to produce immunogenic peptide fragments that can then form stable associations with class II molecules. These two processes, the modification of antigen and its coupling to class II molecules, are thought to occur in acidic endosomal compartments. Furthermore, membrane class II molecules are endocytosed in APC and may provide ligands for the immunogenic peptides. To gain insight into these processes, we examined the internalization and acidification of membrane HLA-DR molecules by three APC populations: 1) freshly isolated Langerhans cells (LC), 2) LC after 48-72 h of bulk epidermal cell culture, and 3) peripheral blood monocytes (PBM). Using FITC-conjugated anti-HLA-DR monoclonal antibodies (MoAb), endocytosis was studied by fluorescence microscopy and by flow cytometry (pulse width analysis), while acidification was assessed by exploiting the pH sensitivity of fluorescein fluorescence. We observed both freshly isolated LC and PBM to internalize surface HLA-DR molecules into acidic compartments with great efficiency. Endocytosis was inhibited by the addition of azide and 2-deoxy-D-glucose, whereas acidification was partially blocked by treatment with ammonium chloride or chloroquine. The degree of internalization and acidification of HLA-DR molecules was greatly influenced by the degree of Ab cross-linking. On the other hand, cultured LC were capable of internalizing HLA-DR molecules, but were not able to acidify the environments to which these molecules were delivered; this loss of acidification capacity was partially restored by treatment with phorbol 12-myristate 13-acetate.(ABSTRACT TRUNCATED AT 250 WORDS)     

Langerhans cells in the physiopathology of atopic dermatitis

INTRODUCTION. Atopic dermatitis (AD), allergic rhino-conjunctivities and allergic asthma constitute the classical triad of atopic diathesis attended, in many cases, by high serum IgE levels. While the pathophysiology of IgE-mediated allergic respiratory diseases is now better understood, the pathophysiological significance of atopic phenomena in the genesis and control of AD is still far from being clear. Numerous clinical and laboratory data point to a pathophysiological relation between IgE-mediated reactions and AD, but no one yet knows by which mechanism this interaction takes place. Some recent studies suggest that Langerhans cells might well be the missing link. THE LANGERHANS CELLS. Langerhans cells (LC) are dendritic epidermal cells originating in the bone marrow and supposedly belonging to the monocyte lineage. Their circulating precursors, the mechanism of their migration into the epidermis and their relationship with other dendritic cells, such as the interdigitating follicular cells, are controverted. LC express numerous surface markers, such as class I and II HLA, CD1a, CD4 and receptors for complement and IgE Fc fragments. Under normal conditions, LC do not express IgE receptors. Ultrastructurally, LC are characterized by the presence of Birbeck granules in their cytoplasm. Among the presumed functions of LC in the skin, the best documented is the presentation of antigens to T lymphocytes in allergic contact dermatitis. LANGERHANS CELLS IN ATOPIC DERMATITIS. Quantitative studies. Modern immunohistological methods based on the reactivity of monoclonal anti-CD1a antibodies have given results that are sometimes conflicting due to differences in the quantification techniques utilized. However, morphometric enumeration of LC on cryostat sections have shown that their number is about the same in AD and in normal skin. PRESENCE OF IgE BEARING LANGERHANS CELLS IN ATOPIC DERMATITIS. The presence of IgE molecules on the LC surface has been demonstrated in subjects with AD. It must be noted that in atopic subjects IgE bearing Lc are only found in patients with high serum IgE levels. They are absent in asthma patients without eczema, irrespective of their serum IgE levels. Daily applications of corticosteroids on AD lesions result in a decrease of anti-IgE markers on LC after one week and in their complete disappearance after 2 weeks. IN ATOPIC DERMATITIS LANGERHANS CELLS EXPRESS A RECEPTOR SPECIFIC TO Fc FRAGMENTS OF IgE. The exact nature of the receptor for IgE expressed in situ in AD patients is still conjectural. Some authors have been able to demonstrate that the binding of IgE molecules by LC isolated from the skin of atopic patients is inhibited by a monoclonal antibody directed against the low affinity receptor (Fc epsilon R2) of eosinophils and macrophages. This strongly suggests that certain factors induce the expression by LC of an Fc epsilon R2 receptor. IN VITRO INDUCTION OF IgE RECEPTORS ON NORMAL LANGERHANS CELLS...     

In vivo PUVA and UVB sensitivity of various human epidermal Langerhans cell markers (ATPase, HLA-DR and T6)—Dose-response and time-sequence studies

To form a comprehensive view of the UV-sensitivity of human epidermal Langerhans cells (LC), the time-sequence and close response effects of single doses of UVB or 8-methoxypsoralen plus UVA (PUVA) radiation on three different LC surface markers were studied with histochemical and immunohistochemical staining. An increasing PUVA dose from 1 to 10 J/cm² caused an almost linear decrease in the surface enzyme (ATPase) positive LC count, whereas the cell surface antigens (HLA-DR and T6) were rather more resistant, up to a PUVA dose of 5 J/cm². A single dose of 5 J/cm² of PUVA induced an LC depletion that was similar during the 21 days of observation, irrespective of whether the cells were visualized with ATPase staining or with monoclonal antibodies against the cell surface antigens HLA-DR or T6. In each case, the nadir was reached 14 days after irradiation; the average residual LC count was then 57%. The cell counts 21 days after PUVA irradiation were still only approximately 74% of the nontreated skin counts. Langerhans cell depletion induced by an erythemagenic dose of UVB irradiation was swifter and more pronounced than that induced by 5 J/cm² of PUVA but, again, a similar time schedule was recorded with ATPase, HLA-DR and T6 staining.     

Mast cell lines HMC‐1 and LAD2 in comparison with mature human skin mast cells – drastically reduced levels of tryptase and chymase in mast cell lines

Please cite this paper as: Mast cell lines HMC‐1 and LAD2 in comparison with mature human skin mast cells – drastically reduced levels of tryptase and chymase in mast cell lines. Experimental Dermatology 2010; 19 : 845–847. Abstract: To circumvent the costly isolation procedure associated with tissue mast cells (MC), two human MC lines, i.e. HMC‐1 and LAD2, are frequently employed, but their relation to mature MC is unknown. Here, we quantitatively assessed their expression of MC markers in direct comparison to skin MC (sMC). sMC expressed all lineage markers at highest and HMC‐1 cells at lowest levels. LAD2 cells expressed comparable high‐affinity IgE receptor α (FcεRIα) and FcεRIγ but less FcεRIβ than sMC and displayed slightly reduced, but robust FcεRI‐mediated histamine release. Only minor differences were found for total histamine content and c‐Kit expression. Huge, and to this level unexpected, differences were found for MC tryptase and chymase, with sMC >>> LAD2 > HMC‐1. Taken together, HMC‐1 cells represent very immature malignantly transformed MC, whereas LAD2 cells can be considered intermediately differentiated. Because of the minute levels of MC proteases, MC lines can serve as surrogates of tissue MC to a limited degree only.     

Densities,distribution and phenotypic expression of T cells in human fetal skin

T cells are present in normal adult human skin, but their occurrence in fetal skin is unknown. T cell and Langerhans cell (LC) populations were studied using single or double immunohistochemical staining on cryostat-section. Skin samples taken from different body regions of 17 fetuses ranging from 18 to 30 weeks estimated gestational-age (w-EGA), were examined. In all specimens but one, we did not find any epidermal T cell. In contrast, dermal CD3⁺ T cells occurred at all w-EGA. The density of these cells increased with increasing age. Double staining showed that CD3⁺ T cells were predominantly CD4⁺/CD45RA⁺. On the other hand, LC, as assessed by CD1a expression, was evenly distributed within the interfollicular epidermis and papillary dermis at all gestational ages. Analysis of T cell and LC density in different body regions did not show significant topographic differences. We suggest that lack of epidermal T cells, although the LC network was fully represented, might reflect the scarce opportunity of fetal LC to contact foreign antigens in utero.     

OKT6 is not superior to HLA-DR or ATPase as a marker for Langerhans'' cells in normal human epidermis

Previous studies have suggested that HLA-DR⁺/OKT6⁺ (DR⁺T6⁺) and DR^?T6⁺ subsets of Langerhans' cells exist in normal epidermis. Using parallel double-staining techniques on epidermal sheets as well as on frozen sections as a control, we have been able to demonstrate that 97–100% of T6⁺ dendritic cells are DR⁺. This finding suggests that DR T6⁺ and DR^?T6⁺ subsets of Langerhans' cells do not exist. In contrast to T6 monoclonal antibody (mAb) directly labelled with fluorescein isothiocyanate, DR mAb indirectly labelled with rhodamine usually stained Langerhans' cells unevenly in the human epidermal sheets (because Langerhans' cells localize throughout the epidermis); however, this effect became much less conspicuous on 4-μm frozen vertical sections and on thinner epidermal sheets. DR antigen density appears to be similar among Langerhans' cells. The even staining with T6 antibody suggests that ii may have a higher affinity for the T6 antigen than DR antibody has for the DR antigen. In normal skin, no significant difference was found among the three different surface markers of Langerhans' cells. ATPase staining on the epidermal sheet, already used for the double staining, significantly underestimated the presence of Langerhans' cells. Previous studies (Muhlbauer et al., 1982; Harrist et al., 1983) have suggested that not all epidermal Langerhans' cells and indeterminate cells are HLA-DR⁺ and that HLA-DR⁺ OKT6⁺ (DR⁺ T6⁺ and DR^?T6⁺ subsets exist. With a four-step peroxidase-antiperoxidase method using either anti-T6 or anti-DR on separate frozen sections, the ratio of DR⁺ to T6⁺ Langerhans' cells varied from 16% to 60% (Muhlbauer et al., 1982; Harrist et al., 1983). In contrast, by the method of double labelling of epidermal cells with DR and T6, Fithian and colleagues (1981) demonstrated that these two antibodies stained identical cells in tissue section. Vertically sectioned Epon-embedded specimens, however, may not be suitable for the enumeration of Langerhans' cells in skin specimens (Horton, Allen & MacDonald, 1983). Recently, Dezutter-Dambuyant et al, (1984b) reported that about 97% of the labelled dendritic epidermal cells in dispersed human epidermal cell suspensions were DR⁺ T6⁺, but Berman and colleagues (1985) found that only approximately 50% of T6⁺ Langerhans' cells were This discrepancy may be due to the fact that, in the absence of dermis, Langerhans' cells rapidly lose the ability to produce the DR antigen (Czernielewski, Demarchez & Prunieras, 1984; Hefton et al., 1984), and the cell membrane of Langerhans' cells could be damaged by the disaggregating effect of trypsin. Because of these disadvantages, we used parallel double-labelling experiments to enumerate Langerhans' cells on the epidermal sheet. To compare with the above two surface markers of Langerhans' cells, a modified ATPase staining technique was used on the sheet with preceding double stains or on a separate epidermal sheet.     

Human epidermal Langerhans cells undergo profound morphologic and phenotypical changes during in vitro culture

Morphology, phenotype, and enzyme activity of highly enriched (80%) unlabeled human epidermal Langerhans cells (LC) have been studied, with emphasis on changes during a short-term culture of three days in vitro. All freshly isolated LC contained Birbeck granules and expressed high levels of CD1a, CD1c, and MHC class II molecules HLA-DR, -DP, and -DQ. They have a weak to moderate expression of RFD1, C3biR, Fc gamma R, p 150/95, MHC class I molecules HLA-ABC, and of the adhesion molecules LFA-3 and ICAM-1, whereas no expression of LFA-1 and several monocyte/macrophage markers were detected. Human LC undergo profound changes during in vitro culture. Birbeck granules, C3biR, Fc gamma R, and p 150/95 were completely lost and the expression of CD1a and CD1c was markedly decreased or lost. Expression of molecules that have essential functions in antigen presentation remained present at the same level (MHC class II molecules and ICAM-1) or was markedly enhanced (LFA-3 and MHC class I). Highly remarkable was the dramatically enhanced expression of interdigitating cell marker RFD1. The monocyte/macrophage markers initially absent remained absent and the enzyme activity initially present (including ATPase and nonspecific esterase) remained present. In conclusion, the results in this report stress rapid alterations of human LC during in vitro culture, resulting in transformation into cells that have phenotypical characteristics of potent antigen presenting cells that resemble interdigitating cells.     

表皮郎格罕细胞表达高亲和力IgE-Fc受体

为了进一步证实抗Ｆ　ＲＩｍＡｂ特异性地结合至郎格罕细胞（ＬＣ）表面，我们用免疫金标记技术进行了免疫电镜检查。发现５ｎｍ金颗粒不连续性地分布于ＬＣ，而非其它表皮细胞表面，从而证明ＬＣ是抗Ｆｃ　ＲＩ反应性表皮细胞。最后，为了了解ＬＣ的Ｆｃ　ＲＩ基因表达与否，进行了ＰＣＲ试验。结果显示在富集ＬＣ而非去除ＬＣ的表皮细胞悬液中存在Ｆｃ　ＲＩａ、　和　链的转录物。总之，本研究提供了直接证据证明正常人表皮ＬＣ表达Ｆ　ＲＩ。