Density Of Epidermal Langerhans Cells Research Articles

Skin Biopsy Findings in Patients With CMT1A: Baseline Data From the CLN-PXT3003-01 Study Provide New Insights Into the Pathophysiology of the Disorder.

Charcot-Marie-Tooth disease type 1A (CMT1A), the most common form of Charcot-Marie-Tooth diseases, is a demyelinating neuropathy caused by a deletion encompassing the gene coding for PMP22, a myelin protein of the peripheral nervous system. Although myelinated fibers are mostly involved in CMT1A, some patients experience neuropathic pain. We thus investigated whether unmyelinated fibers are lost in CMT1A. Skin biopsies were taken from the distal portion of the leg of 80 patients with CMT1A as part of the PXT30003-01 study and processed for quantification of intraepidermal nerve fiber density (IENFD). Mean IENFD was significantly lower in CMT1A patients than in healthy controls. Although the data were highly dispersed, IENFD tended to decrease with age and was higher overall in female patients and controls than male patients and controls. This study shows that small nerve fibers are affected in CMT1A and that this correlates with pin sensitivity. The density of epidermal Langerhans cells (LCs) was also significantly reduced in CMT1A patients, suggesting the involvement of LCs in neuropathic pain processes. These findings raise several questions concerning the interactions of Schwann cells and LCs with unmyelinated fibers in CMT1A. Moreover, they suggest that factors other than PMP22 gene dosage are involved in small fiber pathology in CMT1A.

Oral administration of paeoniflorin attenuates allergic contact dermatitis by inhibiting dendritic cell migration and Th1 and Th17 differentiation in a mouse model.

Allergic contact dermatitis (ACD) is a hapten-specific CD4(+) T-cells mediated inflammatory response of the skin. Its pathomechanism involves 2 phases, an induction phase and an elicitation phase. Langerhans cells (LCs) and dendritic cells (DCs) in the skin play key roles in presenting low molecular weight chemicals (haptens) to the lymph nodes. Therefore, inhibition of the migration of LCs or DCs and T-cell proliferation is each expected to control ACD disease. To explore the effectiveness of paeoniflorin (PF) on the migration of LCs and T-cell proliferation in vivo, we establish a murine model of ACD, promoted by repeated exposure to an allergen (specifically 1-Chloro-2,4-dinitrobenzene (DNCB)). Administration of PF inhibits DC migration in this DNCB-induced model in the induction phase. As a result, epidermal LC density in the elicitation phase increased in PF-treated mice when compared to PF-untreated mice. At the same time, PF reduced IFN-γ(+)CD4(+) and IL-17(+)CD4(+) T cells proliferation (but not IL-4(+)CD4(+) T cells proliferation), leading to an attenuated cutaneous inflammatory response. Consistent with this T-cell proliferation profile, secretions of IFN-γ and IL-17 were reduced and IL-10 secretion increased in PF-treated mice, but production of IL-4 and IL-5 remained unchanged in the skin and blood samples. These results suggest that oral administration of PF can treat and prevent ACD effectively through inhibition of DC migration, and thus decrease the capacity of DCs to stimulate Th1 and Th17 cell differentiation and cytokine production.

Cutaneous immunopathology of long-standing complex regional pain syndrome.

Both increased mast cells numbers and raised immune mediator concentrations indicate immune activation in the affected skin of patients with early complex regional pain syndrome (CRPS), but little is known about regional immune cell involvement in late-stage CRPS. The aim of the current study was to determine skin immune cell populations in long-standing CRPS. Using 6-mm skin punch biopsies from CRPS-affected and non-affected tissues, and a combination of chemical and immunofluorescence staining, we examined the density and function of key cell populations including mast cells, epidermal Langerhans cells (LCs) and tissue resident T-cells. We found no significant differences in either overall immune cell infiltrates, or mast cell density between CRPS-affected and non-affected sub-epidermal tissue sections, contrasting recent findings in early CRPS by other groups. However, CD1a(+) LC densities in the epidermal layer were significantly decreased in affected compared to non-affected CRPS limbs (p<0.01). T-cell clones isolated from CRPS-affected sub-epidermal tissues displayed a trend towards increased IL-13 production in ELISPOT assays when compared to T-cells isolated from non-affected areas, suggesting a Th2 bias. Immune cell abnormalities are maintained in late-stage CRPS disease as manifest by changes in epidermal LC density and tissue resident T-cell phenotype.

Epidermal Ia Bearing Langerhans Cell Density after Steroid Applications: Comparison between Single and Multiple Dosage Regimens

Epidermal Ia Bearing Langerhans Cell Density after Steroid Applications: Comparison between Single and Multiple Dosage Regimens

The tumour necrosis factor-alpha inhibitor adalimumab rapidly reverses the decrease in epidermal Langerhans cell density in psoriatic plaques

The pathophysiology of psoriasis is poorly understood, and the mechanism of action of biological agents interfering with tumour necrosis factor (TNF)-alpha that improve psoriatic plaques is completely unknown. To begin to unravel the mechanism of action, cellular changes occurring in plaques following administration of adalimumab, a humanized monoclonal antibody against TNF-alpha, were investigated. Thirteen different patients underwent sequential biopsies as part of a clinical trial. Each biopsy was immunostained and evaluated to calculate the relative density of epidermal Langerhans cells (LCs) before and after treatment (days 2, 7, 28, 84). To explore the basis for reduced epidermal LC densities in plaques, a SCID-Hu animal model was utilized. Acute psoriatic lesions were created within 2 weeks by injection of superantigen-activated CD4+ T cells into engrafted symptomless skin. Compared with symptomless skin, untreated plaques had a significantly reduced density of epidermal LCs. There was a rapid increase in density of epidermal LCs in plaques following treatment with adalimumab beginning as early as day 7. The paucity of epidermal LCs in plaques was contrasted to the prominent density of LCs in other skin disorders with chronic inflammation and alterations in keratinization, including lichen planus and inflamed seborrhoeic keratosis. Rapid creation of plaques using the SCID-Hu model was accompanied by loss of epidermal LCs, indicating that diminished LC density occurs at an early stage of lesion formation. These data shed light on a new immunopathological perspective highlighting a rapid loss of epidermal LCs in acute psoriatic lesions, with sustained decreased density of LCs in chronic plaques. Furthermore, an unexpected insight into the mechanism of action was uncovered for adalimumab, in which rapid restoration of epidermal LC density was observed.

Impaired contact hypersensitivity in macrophage migration inhibitory factor-deficient mice.

To determine whether macrophage migration inhibitory factor (MIF) is required for contact hypersensitivity (CHS) response, MIF-deficient (MIF KO) and wild-type (WT) mice were sensitized with trinitrochlorobenzene (TNCB) or oxazolone on their abdominal skin and challenged on the dorsum skin of one ear 5 days later. Significant ear swelling was observed in the WT mice, but this response was inhibited in the MIF KO mice (p<0.01 for MIF KO vs. WT mice in 24 h). In addition, lymph node cells from hapten-sensitized MIF KO mice showed a decreased capacity for transferring the CHS response. A topical application of TNCB (200 microg) caused a significant decline in epidermal Langerhans cell (LC) density (20.3%; p<0.01 compared with vehicle) 4 h after application in WT mice, but it failed to provoke a significant epidermal LC migration in MIF KO mice (7.4%). By mixed lymphocyte reaction, the T cell proliferative response to alloantigen was significantly decreased in the MIF KO mice compared with WT mice (p<0.005). Taken together, these results indicate that MIF is pivotal in the regulation of cutaneous immune responses and plays a central role in LC migration and T cell proliferation for the CHS response.

Nitric Oxide-Mediated Depletion of Langerhans Cells from the Epidermis May Be Involved in UVA Radiation-Induced Immunosuppression

Ultraviolet A (UVA) irradiation of the dorsal skin of mice reduced the contact hypersensitivity (CHS) response and the density of epidermal Langerhans cells (LC). The roles of nitric oxide (NO) and reactive oxygen species (ROS) in these biological effects of UVA were investigated. Topical application of NG-monomethyl-l-arginine acetate, an inhibitor of NO production, 2,2′-dipyridyl, an iron chelater, or 4-hydroxy-tempo, a superoxide dismutase mimicking agent, inhibited UVA-induced suppression of the CHS response. NG-monomethyl-l-arginine acetate but not the ROS inhibitors prevented UVA from reducing LC numbers in the epidermis. This suggests that NO but not ROS produced in response to UVA mediates a depletion of LC from the epidermis, probably by signaling these cells to migrate from the skin. This could be responsible for UVA-induced immunosuppression. UVA-induced ROS can also cause immunosuppression, but by a different mechanism. Agents that inhibit or modulate NO or ROS production may be useful for preventing damage caused by the UVA component of sunlight to the skin immune system.

Ultraviolet AI exposure of human skin results in Langerhans cell depletion and reduction of epidermal antigen-presenting cell function: partial protection by a broad-spectrum sunscreen.

Ultraviolet (UV) B-induced effects on the skin immune system have been extensively investigated, but little is known regarding the immunological changes induced by UVA exposure of human skin. Recent data assessing the protection afforded by sunscreens against photoimmunosuppression stress the need for broad-spectrum sunscreens with an adequate UVA protection. The purpose of this study was first to determine the changes observed in epidermal Langerhans cells (ELC) density and epidermal antigen-presenting cell (APC) activity after exposure of human skin to UVAI (340-400 nm) radiation, and secondly to assess the immune protection afforded in vivo by a sunscreen formulation containing a long wavelength UVA filter with a low UVA protection factor (UVA-PF = 3). Epidermal cell (EC) suspensions were prepared from skin biopsies 3 days after exposure to a single dose of UVAI (either 30 or 60 J cm(-2)). Flow-cytometric analysis of EC suspensions revealed that exposure to 60 J cm(-2) UVAI resulted in a decreased number of ELC without infiltration of CD36+ DR+ CD1a- antigen-presenting macrophages into the epidermis, and a significant reduction of HLA-DR expression on viable ELC. In vivo exposure to both 30 and 60 J cm(-2) resulted in a decreased allogeneic CD4+ T-cell proliferation induced by UVAI-irradiated ECs. The sunscreen application partially prevented (57 +/- 9%) the decrease in epidermal allogeneic APC activity induced by 60 J cm(-2) UVAI. In vivo UVAI exposure of human skin results in a decreased number of ELC and in a downregulation of epidermal APC activity. This last effect is partially prevented by prior application of a sunscreen with a low UVAI-PF value. These results indicate that increasing the absorption of UV filters for long UVA wavelengths may lead to an improved immune protection.

]FREQUENCY EPIDERMAL LANGERHANS CELLS IN SITE OF INTRADERMAL INJECTION PROMASTIGOTES OF Leishmania braziliensis IN MICE

ABSTRACT We utilized immunostaining assay with Avidin Biotin Peroxidase (ABP) technique and primary rat monoclonal antibody NLDC-145 specific for mouse dendritic cell, characterized Langerhans cells (LC) in epidermis sheet of 1 mm2 of skin of the footpads of inbred females BALB/c mice, intradermally (id) injected with 1.103 cultured promastigotes of Leishmania braziliensis. The result showed that the injection of the parasites in the skin of the animals produced a progressive increment of epidermal LC in the site of the previous injection, and statistically significant (P<0.05) in each study period. The density of epidermal LC was going up by parasite insult in early time, after the 15 minutes (m) post-infection (pi) with 162± 31.2 LC/mm2, reaching a maximal value of 4503± 713 LC/mm2 to 2 week (w) pi until 898± 481 LC/mm2 to 6 w pi. The number of LC was always higher in epidermis sheet of mice infected with L. braziliensis, than in the epidermis of the control healthy mice, these skin samples showed 120± 28.9 LC/mm2. Morphological changes of the promastigotes injected could to be detected in skin Giemsa-stained imprints, the parasite showed form ovoid and a short flagel, between 15 m and 2 hour (hr) pi. No parasites were even seen in the imprint samples than of any other time of infection. These samples also showed many inflammatory cells, such as: activated macrophages (33%) to 15 m pi, neutrophils (46.33%) to 4 hr pi, eosinophils (2.33%) to 4 hr pi, lymphocytes (15.67%) to 6 hr pi, degraded lymphocytes (8.33%) to 1 w pi, monocytes (4.33%) to 5 day (d) pi and activated monocytes (19.33%) to 1 d pi. The stained sections of skin inoculated, revealed amastigotes into macrophages dermal near of the perivascular area and inflammatory process in the dermis consisted of lymphocytes, monocytes, plasma cell and polymorphonuclear cells between 1 w and 6 w pi. No parasites were detected in the epidermis. The results showed that the promastigotes in the skin survived the first 2 hr out of the macrophages, and on the other hand, stimuled various cell types in site of injection of the parasites, and the proliferation of antigen presentation by epidermal Langerhans cells, necessary for the initiation of the specific T cell immune response.

Alpha-Tocopherol, an inhibitor of epidermal lipid peroxidation, prevents ultraviolet radiation from suppressing the skin immune system.

We investigated the involvement of epidermal lipid peroxidation in the induction of ultraviolet radiation (UVR)-induced suppression of the skin immune system. The shaved dorsal skin of C3H/HeJ mice was irradiated with one of two subinflammatory solar-simulated UVR protocols 3 days per week for 4 weeks. Then half of 1 mg, 1, 2.5 or 5 mg alpha-tocopherol in a vehicle of acetone was topically applied to the shaved dorsal skin before UVR, A 5 mg dose of vitamin E gave complete protection against a UVR protocol that induced a 55% reduction in the contact hypersensitivity response to 2,4,6-trinitrochlorobenzene and a 23% reduction in epidermal Langerhans cell density. Lower doses were ineffective. alpha-Tocopherol was unable to protect against a higher UVR protocol. As 5 mg alpha-tocopherol did not prevent postirradiation inflammatory edema it is unlikely that the antioxidant acted as a sunscreen. However, 5 mg alpha-tocopherol inhibited UVR-induced epidermal lipid peroxidation, suggesting that this may be one mechanism by which alpha-tocopherol prevented UVR-induced local immunosuppression. Scavenging of UVR-generated lipid peroxides and reactive oxygen may have inhibited loss of cell membrane integrity preventing depletion of LC numbers, thus protecting from local immunosuppression.

Influence of epidermal permeability barrier disruption and Langerhans' cell density on allergic contact dermatitis.

Previously, we have showed that artificial epidermal permeability barrier disruption leads to an increase in epidermal Langerhans' cell (LC) density within 24 h. We now asked if this is accompanied by an enhancement of allergic contact dermatitis. Barrier disruption was induced by acetone on the upper arms in 6 volunteers with known sensitization to nickel, fragrance mix, or p-phenylenediamine. Twenty-four hours after this treatment the relevant allergen was applied without occlusion or with Finn chambers. Twenty-four hours after application of the allergen, clinical grading and transepidermal water loss (TEWL) measurements were performed and biopsies were taken. Immunohistochemical stainings for LCs (anti-CD1a, Leu6) and for epidermal proliferation (Ki-S3) were performed. Open applications of the allergens after acetone pretreatment resulted in strong allergic test reactions. TEWL, which showed a 70% recovery 24 h after acetone treatment, was increased again 4-fold by the allergic test reactions. LC density, which was increased by 80% 24 h after acetone-induced barrier disruption, was further enhanced 2.4-fold in total. Epidermal proliferation showed a 6-fold increase after open application of the allergens. Under patch test conditions after acetone pretreatment very strong bullous reactions were observed. We conclude that the increase in epidermal LC density induced by epidermal permeability barrier disruption is accompanied by an enhanced response in allergic contact dermatitis.

HIV-Infected Langerhans Cells Constitute a Significant Proportion of the Epidermal Langerhans Cell Population Throughout the Course of HIV Disease

Human immunodeficiency virus (HIV) is known to infect Langerhans cells, but controversy still exists about the occurrence of HIV-infected Langerhans cells in the skin of HIV-infected individuals and about the density of epidermal Langerhans cells during the course of HIV disease. In this study, epidermal Langerhans cell population densities were analyzed quantitatively in serial biopsies from two burn patients acquired over an 11-y period following infection with HIV from transfusions received during their acute treatment. At each biopsy time point, the density of epidermal Langerhans cells and the proportion that were infected with HIV were analyzed by immunostaining. In both patients, skin grafts were slow to repopulate with Langerhans cells and did not attain normal Langerhans cell densities until about 2 y after grafting. Thereafter, Langerhans cell densities remained within normal limits with the exception of six biopsies at random times that showed a supernormal number of epidermal Langerhans cells. HIV-infected Langerhans cells were first detected at about 2 y post-infection and comprised about one-third of the Langerhans cell population. At subsequent times, HIV p24-stained Langerhans cells were identified in most biopsies and typically constituted about one third to one half of the total Langerhans cell population. The findings show that HIV-bearing Langerhans cells constitute a significant proportion of the epidermal Langerhans cell population over long periods of asymptomatic disease but are unevenly distributed throughout the skin. Normal population densities of epidermal Langerhans cells are maintained for years, although transient increases may occur randomly.

Investigation of notalgia paraesthetica using laser Doppler velocimetry and immunohistochemistry before and after treatment with topical capsaicin

Background Notalgia paraesthetica is an uncommon sensory neuropathy of unknown aetiology that appears to be mediated by peptidergic nerves.Objective To investigate both functional and anatomical aspects of notalgia paraesthetica using laser Doppler velocimetry and immunohistochemistry and to assess the effect of treatment on these parameters.Methods Basal blood flow and response to local heating were recorded in 7 patients with notalgia paraesthetica from within the affected area and the contralateral side as control. Biopsies were taken from both sites for immunohistochemistry with S100 protein, PGP9.5 and CD1a. Measurements were repeated after treatment with topical capsaicin.Results All patients benefited from capsaicin treatment suggesting that the symptoms of notalgia paraesthetica are mediated by peptidergic sensory nerves. Basal blood flow and response to local heating were generally reduced in the affected areas prior to treatment but this did not achieve statistical significance. These differences were less obvious following treatment. The density of CD1a immunoreactive epidermal Langerhans cells and small nerve fibres in the upper dermis both appeared to be slightly increased in the majority of patients within the affected area. No significant change was noted in 3 patients who were rebiopsied after treatment.Conclusions We conclude that in notalgia paraesthetica there is a localised functional abnormality of peptidergic sensory nerves. The relevance of the subtle histological findings is unclear.

Investigation of notalgia paraesthetica using laser Doppler velocimetry and immunohistochemistry before and after treatment with topical capsaicin

AbstractBackground Notalgia paraesthetica is an uncommon sensory neuropathy of unknown aetiology that appears to be mediated by peptidergic nerves.Objective To investigate both functional and anatomical aspects of notalgia paraesthetica using laser Doppler velocimetry and immunohistochemistry and to assess the effect of treatment on these parameters.Methods Basal blood flow and response to local heating were recorded in 7 patients with notalgia paraesthetica from within the affected area and the contralateral side as control. Biopsies were taken from both sites for immunohistochemistry with S100 protein. PGP9.5 and CD la. Measurements were repeated after treatment with topical capsaicin.Results All patients benefited from capsaicin treatment suggesting that the symptoms of notalgia paraesthetica are mediated by peptidergic sensory nerves. Basal blood How and response to local heating were generally reduced in the affected areas prior to treatment but this did not achieve statistical significance. These differences were less obvious following treatment. The density of CD1a immunoreactive epidermal Langerhans cells and small nerve fibres in the upper dermis both appeared to be slightly increased in the majority of patients within the affected area. No significant change was noted in 3 patients who were rebiopsied after treatment.Conclusions We conclude that in notalgia paraesthetica there is a localised functional abnormality of peptidergic sensory nerves. The relevance of the subtle histological findings is unclear.

Superantigen-Induced Langerhans Cell Depletion Is Mediated by Epidermal Cell-Derived IL-1α and TNFα

The purpose of this study was to examine the role of cytokines in staphylococcal enterotoxin-A (SEA)-induced epidermal Langerhans cell (LC) depletion. This was accomplished by analyzing the effect of SEA on cytokine secretion by cultured epidermal cell populations by means of ELISA and by assessing the capacity of cytokines and cytokine-specific antibodies to affect epidermal LC density (as measured by immunoperoxidase staining of epidermal cells bearing surface Ia). The results of this study indicate that SEA induces the secretion of IL-1α and TNFα by epidermal cells, that these cytokines induce LC depletion from epidermis, and that antibodies specific for these agents inhibit the depletion of LC by SEA. Taken together, these findings suggest that IL-1α and TNFα may play essential roles in SEA-mediated depletion of LC from murine epidermis.

Does HIV disease progression influence epidermal Langerhans cell density?

Langerhans cells (LC) are antigen-presenting CD4+ dendritic cells in the skin which may become infected by the human immunodeficiency virus (HIV). Decreased LC function could account for the cutaneous manifestations seen in HIV disease. Previous studies of epidermal LC density in HIV-infected subjects have produced conflicting results. A definitive, prospective, case-control study was performed to determine whether there is an association between epidermal LC density and HIV clinical disease stage. Skin cryosections were stained with the CD1 monoclonal antibody using a three-step immunoperoxidase method. LC were counted by light microscopy and epidermal dimensions calculated with computer-assisted planimetry. The stage of the HIV clinical disease correlated with epidermal LC densities was quantified by three different methods: mean LC numbers per mm length of basement membrane, mean LC per mm2 of epidermal area, and mean LC population per mm of epidermal surface length. Seventy-one subjects, recruited from a large out-patient HIV clinic in London, comprised 56 HIV-positive men and 15 male HIV-negative controls. Contrary to previous smaller studies, there was no detectable association between epidermal LC density (quantified by any of the three methods) and the stage of the HIV clinical disease. Given that HIV infects large numbers of CD4+ cells, we propose possible hypotheses to account for the apparent preservation of static LC numbers in the skin. Further studies of LC kinetics and function are required to elucidate their role in the natural history of HIV infection.

Sodium lauryl sulfate effect on the density of epidermal Langerhans cells. Evaluation of different test models.

The effect of different test models for sodium lauryl sulfate (SLS)-induced irritant contact dermatitis on epidermal Langerhans cells (LC) numbers was examined. Finn Chambers, 8 and 12 mm, containing 15 and 34 or 50 microliters, respectively, of 1% aq. solution of SLS were applied to human forearm skin for 48 h as single or repeated application. The results showed a clear difference between the effects with the 2 chamber sizes. The effect of the 8-mm chambers could result in increased, unchanged or decreased LC numbers, while 12-mm chambers always produced a decrease. These results seem to explain, at least partly, the discrepant results reported from various laboratories.

Does HIV disease progression influence epidermal Langerhans cell density?

Does HIV disease progression influence epidermal Langerhans cell density?

Integrity of the permeability barrier regulates epidermal Langerhans cell density

Previous studies have shown that barrier requirements regulate epidermal liquid and DNA synthesis. In the present study, we examined the possibility that the integrity of the permeability barrier influences epidermal Langerhans cells involved with the immune response. Barrier disruption was achieved by treatment of human skin with acetone, sodium dodecylsulphate (SDS), or tape stripping, until a 10-20-fold increase in transepidermal water loss was achieved. Serial biopsies were performed 6-168 h after treatment, and Langerhans cells were complexed with anti-CD1a (Leu6) or S-100 antibodies, and visualized with an immunoperoxidase technique. Acetone treatment resulted in an increase in epidermal Langerhans cell density, reaching a maximum of 94% over control (P < 0.01) by 24 and 48 h post-treatment. Following SDS treatment or tape stripping, epidermal Langerhans cell density was increased by 100 and 175% (P < 0.01), respectively. There was a linear correlation between the degree of barrier disruption and the increase in epidermal Langerhans cell density. Studies with the Ki-S3 proliferation-associated nuclear antigen revealed a two- to threefold increase in epidermal proliferation after barrier disruption. The time curves of the increase in Langerhans cell density and the increase in epidermal proliferation were similar, suggesting that there was a coordinate regulation. In contrast with our previous studies employing patch test reactions to allergens or irritants, disruption of barrier function neither resulted in an increased dermal Langerhans cell density, nor influenced T lymphocytes (CD3+, Leu4+), macrophages (KiM8+), ICAM-1 or ELAM-1 expression in the skin. In addition, barrier disruption did not result in either dermal inflammation or epidermal spongiosis. In summary, these findings support our hypothesis that the permeability barrier influences epidermal Langerhans cell density, which is involved in maintaining an immunological barrier.

Turnover and kinetics of epidermal Langerhans cells and their dendritic precursor cells in experimental contact dermatitis. A correlated ultrastructural-morphometric and immunohistochemical evaluation.

The numerical density of epidermal Langerhans cells (LCs) in contact sensitivity and toxic contact dermatitis is still a matter of controversy, mainly due to changes in the phenotypic markers of this antigen-presenting cell during the skin reactions. Since the electron microscopic detection of Birbeck granules is the most reliable marker for the identification of normal and pathologically altered LCs, we performed an ultrastructural-morphometric time-course analysis to evaluate their epidermal turnover in the earskin of BALB/c mice after painting the ears with the hapten 2,4-dinitrofluorobenzene and the irritant croton oil. The counts revealed degeneration and depletion of epidermal LCs in both allergic and toxic dermatitis. In contrast, a slightly increased number of activated epidermal LCs was found during contact sensitization. All experimental procedures resulted in an enhanced immigration of so-called indeterminate dendritic cells which also became ultrastructurally activated and often showed Birbeck granule-like formations at their cell membrane. Immunohistochemistry with the monoclonal antibody 4F7, a new marker for dendritic precursor cells of LCs, demonstrated a significant increase in these accessory cells in the epidermis. Our results indicate that contact sensitivity and toxic skin reactions are characterized by complex but distinct changes in the turnover, kinetics and cellular properties of epidermal LCs and their dendritic precursor cells.