正常人体表郎格罕氏细胞的分布

郎格罕氏细胞(LC)是一种具有免疫学功能的细胞.     

豚鼠郎格罕细胞光、电镜共用ATP酶组织化学技术探讨

我们结合光镜下ATP酶染色法.摸索出光、电镜共用的LCMg²⁺-ATP酶的组织化学方法,把光镜下LC计数和电镜下ATP酶的活性及细胞超微结构同时显示出来,既解决了电镜下LC难找的问题,又为研究在LC抗原性改变等某些病理情况下LC的变化提供了有效手段.和国外同类方法的最新报道相比,在保存酶的活性和细胞超微结构方面均有其特点.     

疥疮表皮郎格罕氏细胞的光镜和电镜观察

我们用ATP酶染色和透射电子显微镜观察6例疥疮患者的丘疹表皮内郎格罕细胞(LCs).其中4例LCs密度明显降低,有灶性集聚现象,许多LCs的树枝突缩短、减少或消失.3例用透射电子显微镜进行了观察,2例Birbeck颗粒形态异常,1例Birbeck颗粒增多.我们认为LCs在疥疮的免疫病理中起着重要作用.     

皮肤红斑狼疮中的表皮郎格罕细胞

为研究表皮郎格罕细胞(LC)在皮肤红斑狼疮(LE)中的作用,作者通过Dermovac装置作真空诱疱,取其疱顶表皮,用组织化学染色法和间接免疫荧光法分别检测LC的三种表面标志:三磷酸腺苷酶(ATP酶)活性、HLA-DR抗原和OKT-6抗原,以及用混合表皮细胞—淋巴细胞培养测定氚胸腺嘧啶核苷的掺入,检测从皮肤LE病人分离的表皮细胞刺激同种异体淋巴细胞的增殖能力,对皮肤LE病人皮损和非皮损表皮中的LC进行了研究.受检的皮肤LE病人共7例,其中5例为活动性亚急     

花斑癣患者表皮郎格罕细胞的观察

作者采用ATP酶染色方法对10例花斑癣患者皮损表皮内郎格罕细胞(LC)进行了观察,并对4例患者与皮损相对应部位的正常皮肤进行了同样检查.与此同时,取4名正常人胸腹部正常皮肤作对照检查.结果表明:花斑癣皮损表皮内LC密度明显减少,与正常对照组相比,P<0.001,有灶性集聚现象,许多LC的树枝突缩短、减少或消失.4例花斑癣患者与皮损相对应部位的正常皮肤表皮内LC的变化与皮损表皮内LC的变化相类似.作者认为,LC在花斑癣的免疫病理中可能起着重要作用.     

HIV-1感染过程中的郎格罕细胞

条件性感染和肿瘤主要发生于皮肤及邻近的粘膜表面已成为AIDS的特征性表现.HIV-1感染者中,它们的发病大多是由于HIV-1诱导的免疫系统CD4~+细胞数减少,该细胞的减少引起严重的免疫缺陷.但又发现某特定细胞感染HIV-1后并不一定死亡,而有可能改变其基因表达类型.这样最终使该感染细胞发生生长和(或)功能的异常,随之在同一微环境或远隔部位的其它细胞也出现类似的异常.     

Ia antigens on indeterminate cells of the epidermis: immunoelectronmicroscpic studies of surface antigens

An antiserum against human B-lymphoblastoid cell membrane alloantigens (Ia-like antigens) was used to study the presence of such antigens on dendritic cells in human epidermis. Only Langerhans cells and the majority (85%) of so-called indeterminate cells were positively stained, as shown by immuno-electron microscopy. Fifteen percent of the indeterminate cells were negative and were considered to be immature melanocytes. A relationship exists between the indeterminate cell and the Langerhans cell. A proposal is made concerning emigration of Langerhans cells in response to haptenic stimulation, and the immigration of indeterminate cells to restore the status quo.     

Histiocytosis X cells in eosinophilic granuloma express Ia and T6 antigens

Morphologic similarities between histiocytosis X (HX) cells and epidermal Langerhans cells (LC) have led to the hypothesis that HX represents a proliferative disorder of LC. In order to prove the validity of this assumption, we tested single cell suspensions isolated from an eosinophilic granuloma type HX lesion for the presence of various antigenic determinants defined by monoclonal antibodies using an immunoelectron microscopic technique. An anti-Ia reagent reacted with essentially all histiocytic cells and a small portion of lymphocytes whereas plasma cells and eosinophils were negative. T6 antigen, in contrast, was disclosed exclusively on HX cells either with or without Birbeck granules. Pan-T cell-reagent OKT3 reacted only with small lymphocytes. The finding that HX cells from eosinophilic granuloma lesions are the only cells that have the identical surface marker equipment as epidermal LC (Ia antigens, T6 antigen, Fc-IgG, and C3 receptors) strongly supports the concept that these cells are derived from the LC lineage.     

Antigen-presenting cells in essential fatty acid-deficient murine epidermis: keratinocytes bearing class II (Ia) antigens may potentiate the accessory cell function of Langerhans cells.

Essential fatty acid deficiency (EFAD) is a useful model for studying the role of (n-6) fatty acid metabolism in normal physiology. Because cutaneous manifestations are among the earliest signs of EFAD and because abnormalities in the distribution and function of tissue macrophages have been documented in EFAD rodents, we studied the distribution and function of Class II MHC (Ia) antigen-bearing cells in EFAD C57B1/6 mouse epidermis. Immunofluorescence studies revealed 1.9-9.6 (mean +/- SEM = 5.2 +/- 2.6) times more class II MHC (Ia) antigen-bearing epidermal cells in suspensions prepared from EFAD as compared to normal skin. Analysis of epidermal sheets demonstrated similar numbers of dendritic Ia+ and NLDC145+ cells in EFAD and normal epidermis, however. This discrepancy occurred because some keratinocytes in EFAD epidermal sheets expressed class II MHC (Ia) antigens, whereas keratinocytes in normal mouse epidermis did not. Two-color flow cytometry confirmed that all Ia+ cells in normal epidermis are Langerhans (Ia+ NLDC145+) cells, whereas Ia+ cells in EFAD epidermis are comprised of Langerhans cells and a subpopulation of keratinocytes (Ia+ NLDC145-). Similar levels of Ia antigens were expressed on EFAD and normal Langerhans cells. EFAD and normal epidermal cells were also compared in several in vitro assays of accessory cell function. Epidermal cells prepared from EFAD C57B1/6 mice present the protein antigen DNP-Ova to primed helper T cells more effectively than epidermal cells prepared from normal animals. EFAD epidermal cells are also more potent stimulators of T cells in primary and secondary allogeneic mixed lymphocyte-epidermal cell reactions than normal epidermal cells. The functional differences between EFAD and normal epidermal cells do not appear to result from increased cytokine release or decreased prostaglandin production by EFAD epidermal cells. In view of these findings and the observation that the antigen-presenting cell activity of EFAD epidermal cells correlates with the number of Ia+ keratinocytes in epidermal cell preparations, Ia+ keratinocytes (in the presence of Langerhans cells) may potentiate cutaneous immune responses in vitro and perhaps in vivo as well. These results also suggest that (n-6) fatty acids or metabolites of (n-6) fatty acids are involved in regulating the expression of class II MHC (Ia) antigens by keratinocytes in vivo.     

Reduced density and morphologic alteration of Ia and ADPase positive Langerhans cells after low-protein diet

This study examined the effects of low-protein diet on the population density, morphology and histochemical characteristics of Langerhans cells. Weaned at 18 days old, BALB/c mice were divided into two groups: one group received a high-protein diet (20% casein) and the other was fed an isocaloric low-protein diet (caesin 4%). After 14 days, the mice were killed and the skin of the ears was removed for investigation. Langerhans cells were visualized using ADPase and anti-Ia immunoperoxidase techniques. In protein malnourished mice, the density of ADPase and Ia-positive Langerhans cells was significantly reduced, while morphometric assessment of their cross-sectional area showed a significant reduction of total cell area, cell body area and degree of arborization. Quantitative cytophotometric analysis revealed a reduction of ADPase ectoenzyme activity and decreased concentration of membrane Ia antigen. We postulate that these changes affect Langerhans cell functions, and in turn influence the immune mechanisms in the skin.     

Cultured human Langerhans cells process and present intact protein antigens.

Epidermal Langerhans cells (LC) undergo profound phenotypic and functional alterations when cultured for 2 to 3 d. To determine whether the in vitro culture of human LC modulates their capacity to process and present intact protein antigens, we compared the ability of freshly isolated LC (fLC) and cultured LC (cLC) to stimulate in vitro T-cell proliferative responses to recall antigens. We found that human fLC and cLC were able to process and present recall antigens to primed T cells, inducing significant proliferative responses. For tetanus toxoid and Candida albicans extract, T-cell proliferative responses at 6 d to antigen-pulsed fLC were slightly greater than responses to antigen-pulsed cLC. For live influenza A virus, the T-cell responses induced by antigen-pulsed cLC were comparable or slightly greater compared with fLC. Allogeneic T-cell proliferation for both LC preparations were also comparable. The exogenous pathway of antigen processing was demonstrated by chloroquine inhibition.     

Immuno-electron microscopic studies of surface receptors and antigens of human Langerhans cells

A heteroantiserum, prepared in rabbits against fractionated cell membranes of a human B-lymphoblastoid cell line, was used to study the distribution of Ia antigen(s) in human epidermis. Indirect immunofluorescence staining demonstrated specific reactivity of dendritic supra-basal cells, consistent in location with Langerhans cells. Basally located cells were noted in biopsy specimens from vitiliginous skin and from the leukodermatous regions of halo naevi. The specificity of the reaction was confirmed at the ultrastructural level by means of ferritin labelling methods. Cell surface staining was confined in the epidermis to Langerhans cells. Fc and C3' receptors were studied by means of rosetting methods. Negative results were obtained on frozen sections, while 2-3% of cells formed rosettes when applied to an epidermal cell suspension.     

The semi-quantitative distribution of T4 and T6 surface antigens on human Langerhans cells

We have used indirect immunogold electron microscopy to compare the respective density of cell membrane determinants revealed by OKT6 and OKT4 monoclonal antibodies on normal human Langerhans cells (LC): 12.9 +/- 3.5 gold granules were noted per cell section on OKT4-positive LC whereas 236.8 +/- 23.5 granules were counted per cell section on OKT6-reactive cells. These results confirm that human LC react with OKT4 antibody and they demonstrate a marked quantitative difference on LC surface between the antigenic determinants recognized by OKT6 and OKT4 antibodies.     

Immunologic aspects of acute cutaneous graft-versus-host disease: decreased density and antigen-presenting function of Ia+ Langerhans cells and absent antigen-presenting capacity of Ia+ keratinocytes

Cutaneous graft-versus-host disease (GVHD) provides a unique model for studying the pathogenesis of several important lymphocyte-mediated skin diseases. Morphologic studies have suggested that Ia antigen (Ia)-bearing epidermal Langerhans cells (LC) may be specific targets for destruction in these conditions. Keratinocytes synthesize and express Ia in GVHD and some other lymphocyte-mediated skin disorders; Ia+ keratinocytes, constitutively able to secrete epidermal cell-derived thymocyte activating factor (ETAF)/interleukin 1, may possess antigen-presenting capacity, thus leading to enhanced cutaneous immune responses and disease chronicity. We therefore investigated the fate of Ia+ LC, and the potential antigen-presenting capacity of Ia+ keratinocytes, in a murine model of GVHD. Lethally irradiated C3H/He (H-2k) mice developed acute cutaneous GVHD, and expressed keratinocyte Iak, 8 days after injection of BALB/c (H-2d) bone marrow and spleen cells. Immunofluorescence studies showed a progressive decrease in the density of Ia+ epidermal LC during the evolution of GVHD. This decrease was paralleled by a progressive reduction in the allostimulatory capacity of GVHD epidermal cells (EC) in the allogeneic EC-lymphocyte reaction (ELR). The fall in the density of Ia+ LC, and in EC allostimulatory capacity in both primary and secondary ELRs, was consistently greater in GVHD mice than in mice treated only with x-irradiation. The allostimulatory capacity of GVHD and x-irradiated EC could not be restored by addition of indomethacin or exogenous ETAF to ELR cultures. The decreased allostimulatory capacity was not the result of inhibition of the ELR, since EC from GVHD and x-irradiated mice did not cause suppression when added to control ELR cultures. The capacity of EC to present ovalbumin, purified protein derivative of tuberculin, 2,4,6-trinitrobenzenesulfonic acid coupled to EC, and native cytochrome c (CYTc) to antigen-specific T-cell lines, clones, or hybridomas was reduced in x-irradiated mice and markedly decreased in GVHD mice. The capacity of EC from x-irradiated and GVHD mice to present CYTc fragment 81-104, which does not require further processing or catabolism by accessory cells, was similarly decreased. Taken together, the results indicate that: the function of LC is markedly and progressively impaired in acute GVHD; LC function is also decreased, but to a lesser extent, following x-irradiation alone; and Ia+ keratinocytes from lethally irradiated mice undergoing GVHD do not exhibit antigen-presenting capacity.