Immunohistochemical analysis of contact sensitivity reactions in the guinea-pig using novel monoclonal antibodies: the influence of topical cyclosporin A.

When applied topically to guinea-pig skin from the time of epicutaneous antigen challenge, cyclosporin A (CsA) in ethanol:olive oil (1:2) significantly reduced contact sensitivity reactions to dinitrofluorobenzene (DNFB). This immunosuppressive effect was no longer apparent when initial drug administration was delayed for several hours, or when a non-immunosuppressive cyclosporin derivative was applied. Attenuation of skin reactions was accompanied by significant reductions in T cells recognized by putative pan T cell (CT7) and T cytotoxic/suppressor cell (CT6) monoclonal antibodies, whilst there were also concomitant decreases in basophil infiltration. There was no reduction in epidermal Langerhans cells or in infiltrating mononuclear cells recognized by MSGp9 (mainly dendritic cells) in CsA-treated reaction sites. There was no apparent reduction in Ia antigen expression (staining with MSGp8) on intralesional inflammatory cells with CsA treatment. Whilst demonstrating the efficacy of topical CsA in contact sensitivity, our findings suggest that more than one mechanism may be operative in the suppression of these cutaneous inflammatory reactions.     

Immunological activation of dermal Langerhans cells in contact with lymphocytes in a model of human inflamed skin

Langerhans cells play an important role in the skin's immune system. Little is known, however, about the antigen-presenting capacity of Langerhans cells in the context of skin inflammation. By immunohistochemistry we investigated the phenotypic characteristics of epidermal and dermal Langerhans cells and their spatial relationship with infiltrating lymphocytes. We studied skin flaps autotransplanted to the oral cavity to fill a defect after maxillofacial cancer surgery. In 15 of 21 cases sampled for the present study, the skin flaps were severely inflamed by Candida albicans infection. In contrast to the normal skin, such inflamed skin showed a marked increase in CD1a(+) dermal Langerhans cells. Double immunohistochemistry revealed that dermal Langerhans cells abundantly expressed B7-2 (CD86), a representative costimulatory molecule, and CD83, a marker of mature dendritic cells. Furthermore, these dermal Langerhans cells were in close contact with CD4(+)/CD45RO(+) lymphocytes. This cell-to-cell contact was further visualized by immunoelectron microscopy. Langerhans cells were also observed within lymphatic vessels that were identified by the expression of vascular endothelial growth factor receptor-3. Ki-67 labeling indices were 4.2% in CD4(+) T cells and 0.8% in CD8(+) T cells within the dermis. Factor XIIIa(+) dermal dendrocytes were distributed outside the clusters of lymphocytes and were not in contact with them. Our observations indicate that dermal Langerhans cells in the inflamed skin are activated to express common phenotypes to mature dendritic cells so that they could stimulate neighboring memory CD4(+) T cells.     

Histological and ultrastructural effects of cyclosporin A on normal human skin xenografted on to nude mice

Summary Cyclosporin A (CsA) is a potent immunosuppressant with a selective activity on T-helper lymphocytes. However, CsA also exerts biological effects on non-lymphoid cells (fibroblasts, endothelial and epithelial cells). CsA can inhibit in vivo and in vitro DNA synthesis of epidermal keratinocytes (EK) and induces in vivo morphological alterations of kidney epithelial cells. In the present study we investigated the in vivo effects of a short-term CsA treatment (50 mg/kg per day) on DNA synthesis (evaluated through 5-bromo-2-deoxyuridine incorporation) and on the histological features of normal human skin xenografted (NHSX) on to congenitally athymic nude mice. When compared with control NHSX, CsA induced a statistically significant inhibition of DNA synthesis of NHSX EK. At the light- and electron-microscopic level, apart from a decrease in the thickness of the viable epidermis of NHSX (statistically non-significant), no noticeable differences between treated and control NHSX could be detected. EK, Langerhans cells and melanocytes appeared morphologically unaffected by CsA and no signs of acute toxicity (giant mitochondria, vacuolization, microcalcifications) were seen. These results suggest that CsA exerts a subtle effect on human EK; indeed, despite an unequivocal antiproliferative activity, no significant histological changes related to the acute CsA toxicity seem to be induced on the various epidermal cell types.     

Inhibition of contact sensitivity reactions to DNFB by topical cyclosporin application in the guinea-pig.

Contact sensitivity skin reactions to dinitrofluorobenzene (DNFB) were inhibited by twice daily topical application of cyclosporin (CsA, 2%) in normal guinea-pigs and in those with enhanced contact sensitivity reactions following pre-treatment with cyclophosphamide. In contrast to oral administration of CsA (25 mg/kg) for 4 days, topical application of the drug over the same period did not result in systemic absorption (as measured by radioimmunoassay) or in any evidence of nephrotoxicity.     

Antigen presentation in the skin: modulation by u.v. radiation and chemical carcinogens.

The skin provides an excellent model to investigate antigen presenting cells (APC) particularly using contact hypersensitivity responses. The skin has its own distinct APC of which Langerhans cells (LC) are the best characterized. Fluorescein isothiocyanate (FITC) has proved a useful reagent with which to follow antigen-labeled APC to draining lymph nodes, where they bind to T lymphocytes. Cluster formation appears to be a necessary component of the APC-T cell interaction. Both u.v. radiation and chemical carcinogens are able to alter LC in the skin, resulting in immunological tolerance when antigen is presented through such treated sites. The changes in APC function are linked mainly to the tumor promoting action of carcinogens. The nature of the APC that trigger suppressor circuits and the potential chemical mediators involved are discussed. These studies have important implications for the immunobiology of the skin and for cutaneous carcinogenesis.     

Augmentation of delayed-type hypersensitivity to high dose sheep erythrocytes by cyclosporin A in the mouse: influence of drug dosage and route of administration and analysis of spleen cell populations.

When administered by various routes 48 h before a high systemic dose (10 degrees) of sheep red blood cells (SRBC), Cyclosporin A (CsA) prevented the suppression of delayed-type hypersensitivity (DTH) reactions elicited 4 days later. Augmentation of DTH was observed over a wide range (5-200 mg/kg) and with circulating CsA levels ranging below 45 ng/ml at the time of immunization or antigen challenge. Splenic lymphocytes from vehicle- and CsA-treated mice exhibited good proliferative responses to mitogen in vitro, but only those from CsA-treated animals responded to antigen. Expression of DTH was associated with a progressive, 2-fold increase in the absolute numbers of splenic L3T4+ cells, whereas no significant alteration in the number of Lyt-2+ lymphocytes was recorded. B cell and macrophage numbers in the spleen were unaffected by CsA. In contrast to its potentiating effects on cell-mediated immunity, CsA caused profound (up to 100%) suppression of the concomitant production of splenic anti-SRBC IgM-secreting plasma cells. Circulating anti-SRBC antibody levels were also markedly reduced. These data show that CsA can permit induction of TDTH, whilst suppressing T-dependent humoral immunity and without significant change in absolute numbers of Lyt-2+ cells.     

Role of Langerhans cells and Thy. 1+ effector cells in herpes simplex virus-1 infection in the skin of newborn mice

Summary Langerhans cells function in the epidermis as very potent accessory cells. Their role as antigen-presenting cells in the immune response following herpes simplex virus type 1 (HSV-1) skin infection of newborn mice was studied. Newborn C 57 BL/6 mice were found to be susceptible while adult mice are resistant to HSV-1 infection in the skin. Because the immune response to HSV-1 infection in the skin is mainly cell-mediated, and therefore dependent on the presence of functional accessory cells, the state of Langerhans cells in the skin of newborns was studied. Staining of whole epidermal mounts revealed similar numbers of Ia⁺ and ATPase⁺ Langerhans cells in the epidermis of newborn and adult mice. In a skin lymphocyte reaction assay, Langerhans cells derived from newborn mice were shown to stimulate proliferation of T cells derived from adult allogeneic mice to the same degree as adult-derived Langerhans cells. HSV-1 was injected into the skin of C 57 BL/6 newborn mice together with various preparations of adult-derived spleen cells devoid of antigen-presenting cells. The injected adult-derived lymphocytes were found to confer protection against HSV-1 infection in newborn mice, despite the lack of detectable antigen-presenting cell (APC) function in this cell preparation. The cell subset involved in the transfer of resistance was found to be Ia^– and Thy. 1⁺.     

Langerhans cells and dermal dendritic cells capture protein antigens in the skin: Possible targets for vaccination through the skin

Dendritic cells capture and process antigen and present it to T lymphocytes in the lymphoid organs. Dendritic cells of the skin, including epidermal Langerhans cells, langerin⁺ and langerin^negative dermal dendritic cells are ideally positioned to take up pathogens that enter the body through the skin or vaccines that are administered into (intradermal) or onto (epicutaneous) the skin. The antigen uptake properties of skin dendritic cells have not thoroughly been studied yet. We therefore investigated the uptake of the fluorochrome-conjugated model antigen ovalbumin (OVA) by skin dendritic cells in the mouse. OVA was readily taken up by immature Langerhans cells both in situ and in cell suspensions. When offered to Langerhans cells in situ either by “bathing” skin explants in OVA-containing culture medium or by intradermal injection they retained the captured OVA for at least 2–3 days when migrating into the culture medium and, importantly, into the draining lymph nodes. Also langerin⁺ and – to a larger extent – langerin^negative skin dendritic cells took up and transported OVA to the lymph nodes. Interestingly, mature Langerhans cells were still capable of ingesting substantial amounts of OVA, indicating that predominantly receptor-mediated endocytosis is operative in these cells. Unlike macropinocytosis, this pathway of endocytosis is not shut down upon dendritic cell maturation. These observations indicate that in intradermal vaccination schemes, Langerhans cells from the epidermis are prominently involved. They were recently shown to possess the capacity to induce functional cytotoxic T lymphocytes. Furthermore, the potential to markedly enhance antigen uptake and processing by targeting antigen to c-type lectin receptors on Langerhans cells was also recently demonstrated. Our data provide a rationale and an incentive to explore in more detail antigen targeting to Langerhans cells with the aim of harnessing it for immunotherapy.     

Anti-CD3 antibody-induced expression of both p55 and p75 chains of the high affinity interleukin-2 receptor on human T lymphocytes is inhibited by cyclosporin A.

The inhibitory effect of cyclosporin (CsA) was investigated on human lymphocytes stimulated by anti-T-cell antibodies (anti-CD3 and -CD2) or mitogenic lectins. Whereas inhibition of cell proliferation (50%) occurred at 10 ng/ml CsA after cell activation via CD3 or CD2, higher CsA concentrations (300 ng/ml) were necessary to inhibit lectin-mediated cell activation (PHA, Con A). Exogenous recombinant interleukin-2 (rIL-2) partially reversed the inhibitory effect on antibody-stimulated cells only; however, at higher CsA concentrations (300 ng/ml) proliferation was again inhibited. Thus, CsA affected IL-2R expression and/or function at higher concentrations (300 ng/ml). CsA had no effect on receptor function as measured on IL-2-dependent cell growth of CTLL cells or preactivated lymphocytes. However, CsA inhibited both high and low affinity receptor expression as shown by [125I]IL-2 equilibrium binding studies on anti-CD3-stimulated cells. Cross-linking studies revealed that both p55 (TAC) and p75 chains of the IL-2R were not induced at low CsA concentrations (10 ng/ml). However, addition of rIL-2 reversed CsA inhibition of IL-2R expression. It is concluded that CsA, at least in anti-CD3-stimulated cells, inhibits IL-2R expression and cell proliferation with similar potency. Exogenous rIL-2 reverses CsA inhibition of IL-2R expression. This might be due to binding of rIL-2 to receptors which escape CsA inhibition, thereby up-regulating receptor expression which is drug resistant.     

Epidermal Langerhans cell density and contact sensitivity in young and aged BALB/c mice

The loss of tissue and organ function with age may depend on the inability of old cells to carry out specialized functions. Like other systems in the body, the immune system deteriorates with age. Over the past 10 years it has become clear that the skin can play an active role in immunological processes. In this report we evaluated changes in murine cutaneous immunity with age. Studies in humans had shown a decreased Langerhans cell density with age, but it is difficult to control for the effect of ultraviolet light in human studies. Since ultraviolet light has a significant effect on Langerhans cells, we chose to evaluate the effect of age on Langerhans cell density using inbred mice not exposed to ultraviolet light. Cutaneous immunity was examined phenotypically by studying Langerhans cell density and functionally by studying allergic contact sensitivity. Langerhans cell density was assessed in epidermal sheets prepared from ear skin of mice and examined by ATPase histochemistry and fluoresceinated anti-Ia staining. With both methods, aged (18 months old) mice had approximately two-thirds the number of Langerhans cells that young (10-12 weeks old) animals did. Allergic contact sensitivity response to trinitrochlorobenzene (TNCB) was compared between aged and young animals. Although the aged animals demonstrated increased variability in their responsiveness, there was no overall difference in this example of cutaneous immunoreactivity between the two age groups.     

HLA class II expression on human epidermal Langerhans cells in situ: upregulation during the elicitation of allergic contact dermatitis.

An immunoelectron-microscopic technique was applied to investigate the localization of molecules that are involved in the elicitation of allergic contact dermatitis in human epidermal cells in situ. Langerhans cells in the epidermis of lesions showed a strongly increased cell surface expression of HLA class II molecules as compared with normal skin. In addition, a high number of intracellularly located HLA class II molecules were present in Langerhans cells of lesional epidermis, suggesting increased biosynthesis of these molecules during the elicitation process. In contrast, no differences in the expression of CD1a by Langerhans cells was observed between normal and lesional skin. Frequently, the Langerhans cells were found in close apposition to mononuclear cells, which also exhibited a strong cell surface HLA class II expression. The number of Birbeck granules that are characteristic intracellular Langerhans cells organelles was increased in lesional Langerhans cells as compared with normal-skin Langerhans cells, which may correlate with the activated state of lesional Langerhans cells. These Birbeck granules were always HLA class II or CD1a negative. The increased synthesis and expression of HLA class II molecules on the cell surface of Langerhans cells suggests a direct role for these HLA class II molecules in the elicitation process of allergic contact dermatitis.     

Phenotypic analysis of guinea pig Langerhans cells with antibodies directed against leucocyte surface antigens

The epidermis was stained with a panel of recently produced anti-guinea pig leucocyte antibodies. Guinea pig Langerhans cells were not detectable with antibodies directed against B lymphocytes (MSgp9), T lymphocytes (CT7 and MSgp7), T-helper/inducer (MSgp12) and putative T-suppressor/cytotoxic (CT6 and MSgp6) subsets. Langerhans cell expressed both major histocompatibility complex (MHC) class-I and II antigens and also an epitope (CT4) associated with lymphocyte migration, thus suggesting the migratory potential of this cell. Although the Langerhans cell did not express macrophage specific antigens, MSgp5, which detects lymphoid dendritic cells, was weakly expressed on the Langerhans cell. The Langerhans cell expressed a leucocyte-common antigen detected by H201. Double-labelling studies with anti-MHC class-II antibodies indicated that only 0.4 +/- 0.3% of the pan leucocyte-positive epidermal cells were Ia-negative, indicating that it is unlikely that a guinea pig analogue of the murine Thy-1 + dendritic epidermal cell (Thy-1 + dEC) exists.     

The role of ICAM-1 molecule in the migration of Langerhans cells in the skin and regional lymph node

ICAM-1 (CD54) plays an important role in the cell-cell interaction and migration of leukocytes. Previous studies have shown that ICAM-1 is involved in inflammatory reactions and that a defect in ICAM-1 gene inhibits allergic contact hypersensitivity. This study indicates that the migration of hapten presenting Langerhans cells into the regional lymph nodes was significantly reduced in ICAM-1-deficient mice compared to wild-type C57BL/6 mice. The reduced number of dendritic cells in regional lymph nodes did not result from abnormal migration of Langerhans cells into the skin of ICAM-1-deficient mice. The concentration and distribution of Langerhans cells in the na?ve skin of ICAM-1-deficient mice was equal to that of wild-type mice. Following hapten sensitization, Langerhans cell migration out of the skin and recruitment of fresh Langerhans cells back to the epidermis was not affected in ICAM-1-deficient mice. Further experiments demonstrated that ICAM-1 deficiency on lymphatic endothelium rather than on dendritic cells was responsible for the reduced migration of Langerhans cells into draining lymph nodes. This study indicates that ICAM-1 regulates the migration of dendritic cells into regional lymph nodes but not into or out of the skin.     

Heterogeneous reactivity of murine epidermal Langerhans cells after application of FITC: a histochemical evaluation

To elucidate the detailed kinetics of epidermal Langerhans cells after topical contact sensitizer stimulation, we examined ATPase or Ia positive epidermal cells of BALB/c mice in a time-spaced manner after the topical application of fluorescein isothiocyanate (FITC). We also performed double labeling of Langerhans cells in epidermal sheets with ATPase activity and Ia antigen or costimulatory molecules (B7-1 and B7-2) after the same stimulation. Observations showed that the density of ATPase positive cells and Ia positive cells decreased following a different time course; the former reached a nadir (77.4% of control) at 4 h but the latter reached a minimum (82.8% of control) at 16 h after the application of FITC. A double labeling technique revealed an increase in Ia single positive cells at 4 h as opposed to that of ATPase single positive cells at 16 h after application. Both costimulatory molecules were expressed on the dendritic processes of many Langerhans cells as a dotty pattern at 4 h after application; B7 positive and ATPase negative areas were observed at this time. On electron microscopic observation, a few activated Langerhans cells found in the dermis at 4 h after application had distinctive profiles compared with residual Langerhans cells in the epidermis. These findings suggest that there is a heterogeneity of reactivity to FITC in epidermal Langerhans cells, and that only a small portion of them migrates from the epidermis during sensitization. The findings also indicate the importance of the interaction between the Langerhans cell and its surrounding microenvironment in the epidermis for its activation. In addition, the results indicate that the enzymatic and the phenotypic markers do not definitively reflect the presence (or absence) of Langerhans cells.     

Langerhans cells: antigen presenting cells of the epidermis

While epidermis in the skin provides an excellent barrier to the environment, it is an incomplete one. Some antigenic material can penetrate through the stratum corneum (or be introduced pathologically) where strategically placed epidermal Langerhans cells reside. In this review, we have assembled relevant data concerning the antigen presenting potential of epidermal Langerhans cells. Strong circumstantial evidence derived from in vitro studies of epidermal cell suspensions enriched for Langerhans cells indicates that Langerhans cells possess this capability. In vivo studies with intact skin indicate that critical numbers of functioning Langerhans cells are essential for successful induction of contact hypersensitivity by epicutaneously applied haptens. And within the past several months, experiments with purified preparations of epidermal Langerhans cells have proven that these cells, and perhaps they alone among epidermal cells, possess the capacity of processing and presenting haptenic determinants to the immune system. The challenge for the future is to determine the extent to which this unique property of Langerhans cells affords physiologic protection to the skin and under what pathologic circumstances altered Langerhans cell function leads to disease.     

Systemic suppression of contact hypersensitivity by UVB radiation is unrelated to the UVB-induced alterations in the morphology and number of Langerhans cells

Exposure of mice to UVB (280-320 nm) ultraviolet radiation reduces contact hypersensitivity (CHS) reactions to chemicals that are applied subsequently to unirradiated skin. It also decreases the number and alters the morphology of Langerhans cells at the site of irradiation. We addressed the question of whether the systemic suppression of CHS was related to these modifications of Langerhans cells by UVB radiation. In mice treated on the dorsum with UVB radiation, the number and morphology of Langerhans cells in the unexposed areas of skin used for inducing and eliciting CHS appeared normal. Therefore, the depression of CHS could not be attributed to a depletion of Langerhans cells at the sites of application of the sensitizing agent. We also examined the correlation between alterations in Langerhans cells and systemic suppression of CHS after treatment with various types of nonionizing radiation. Treatment of mice with UVA (320-400 nm) radiation eliminated detectable Langerhans cells from the exposed skin, based on ATPase staining and electron microscopy, but did not reduce CHS; in fact, CHS was enhanced in these animals. Neither rose bengal nor eosin, in combination with visible (greater than 400 nm) radiation, affected the number or appearance of Langerhans cells, even though microscopic evidence of phototoxicity was present. However, rose bengal plus visible radiation depressed CHS reactions that were induced and elicited through unexposed skin. Depletion of Langerhans cells from dorsal skin by exposure to UVA radiation did not prevent suppression of CHS by subsequent exposure of the Langerhans cell-depleted skin to UVB radiation. We conclude that systemic suppression of CHS by UVB irradiation is not related to the numerical and morphological alterations in Langerhans cells that occur locally at the site of irradiation.     

CD23/Fc epsilon R11 expression in contact sensitivity reactions: a comparison between aeroallergen patch test reactions in atopic dermatitis and the nickel patch test reaction in non-atopic individuals.

The immunopathology of patch test reactions to aeroallergens in patients with atopic dermatitis (AD) has been compared to that of contact sensitivity reactions to nickel in non-atopic individuals. Both reactions were found to exhibit equivalent erythema and induration on gross examination at 48 h. Four millimetre punch biopsies were obtained at 48 h frozen, and cryostat sections stained with a panel of MoAbs. The distribution of macrophages, dermal dendritic cells, Langerhans cells, T lymphocytes and the expression of CD23 antigen was recorded. Increased numbers of dermal dendritic cells, macrophages, T lymphocytes and Langerhans cells were found in the dermal infiltrates of both the nickel patch test reactions and the aeroallergen patch test reactions compared with their respective controls. There were no significant differences between atopic patch test reaction and nickel patch test reaction samples in the tissue distribution of these cell types. There was a significant increase in CD23 expression on Langerhans cells and dermal dendritic cells in the atopic patch test reactions, whereas an increase was only observed on dendritic cells in nickel patch test reactions. No significant difference in CD23 expression was observed in the control skin samples taken from patients with AD, nickel-sensitive patients and normal controls. This study supports the hypothesis that the aeroallergen patch test reaction in atopic dermatitis is a delayed hypersensitivity reaction, yet is distinct from the contact sensitivity reaction to nickel in terms of raised expression of CD23.     

Morphologic and Morphometric Study of the two Main Cell Lineages Involved in Mycosis Fungoides: The Lymphoid Cells and the Langerhans Cells

A comparative light and electron microscopic study was carried out on skin biopsies from 5 mycosis fungoides patients (stages II and III). In addition, certain zinc-iodide-osmium (ZIO) procedures that selectively reveal the Langerhans cells (LC) were also applied. Several morphometric analyses, such as relative frequency, cell size, nuclearxell ratios and nuclear contour indexes, were performed.

Two main cell lineages were found in the dermal infiltrate: the lymphoid cells, represented by lympho-blastlike cells (LB), lymphocytes (L), and mycosis fungoides cells (MFC), and the Langerhans cells. A pattern of cellular organization of the dermal infiltrate was recognized. The LC appeared as the “organizing” cell. The morphometric study indicated that all LB, L, and MFC have the chance, at the same time, to be in contact with a LC. The application of the ZIO procedures clearly indicated a “translocation” of the LC, since they were scarce or absent from the epidermis and numerous in the dermis. Evidence is presented indicating that differentiation of LB into L and malignant transformation of L into MFC are processes occurring predominantly in the dermis.

It is postulated that in the chronic stages of mycosis fungoides, L-LC contacts occur mainly in the dermis and not in the epidermis and that the development of malignant clones may occur in the dermis.     

Topical tacrolimus and cyclosporin A differentially inhibit early and late effector phases of cutaneous delayed-type and immunoglobulin E hypersensitivity

Systemic and topical administration routes of tacrolimus and cyclosporin A (CsA) were compared in effects on early and late phases of elicited T-cell-mediated contact sensitivity (CS), and effects on early and late phases of cutaneous immunoglobulin E (IgE) antibody-mediated hypersensitivity responses in mice. Thus, both CS and IgE responses in the skin have an early mast-cell-dependent phase, and also a late inflammatory phase. We measured the effects of both immunosuppressants on both phases of the respective T cell versus IgE responses. Systemic administration of both agents completely suppressed CS and IgE late-phase responses, but failed to affect either early phase. In contrast, when topical CsA was used, low doses abolished the early phase of IgE responses, but even high doses did not inhibit the early phase of CS. Conversely, topical tacrolimus inhibited the early phase of CS more potently than the early phase of cutaneous IgE hypersensitivity responses. Thus, topical treatment was needed to inhibit the early phases and the two agents acted differentially, suggesting differing susceptibility of the early phases, that are probably due to different signalling mechanisms. These studies underscore the potential value of topical administration of these powerful immunosuppressive agents in the treatment of allergic diseases that exhibit features of early-phase mast-cell-dependent inflammation, and late inflammation due to mast cells or to T cells, such as atopic dermatitis or asthma, since the early phase is predominantly susceptible to topical application, while the last phase of both IgE and T-cell inflammation responds to systemic treatment with both agents.     

The Langerhans Cell: Sentinel of the Body's Immune Defense System. I. Morphology and Microscopic Methods of Detection

Abstract

The Langerhans cell (LC), although found in the skin, is one of the cells of the lymphoid system; it is believed to originate in the bone marrow. The LC wanders to other parts of the body, where it plays an important part in the immune response by helping to present antigen to T lymphocytes. Langerhans cells are differentiated from macrophages, melanocytes, T lymphocytes, and interdigitating cells by a number of markers, the most useful being OKT-6/Leu6 and the Birbeck granule. (The J Histotechnol 10: 121, 1987).