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Epidermal Langerhans Cells (epidermal + langerhan_cell)
Selected AbstractsEpidermal Langerhans Cells Promote Skin Allograft Rejection in Mice With NF-,B-impaired T CellsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2008L. L. Molinero T cells play a major role in the acute rejection of transplanted organs. Using mice transgenic for a T-cell-restricted NF-,B super-repressor (I,B,,N-Tg mice), we have previously shown that T-cell-NF-,B is essential for the acute rejection of cardiac but not skin allografts. In this study, we investigated the mechanism by which skin grafts activate I,B,,N-Tg T cells. Rejection was not due to residual T-cell-NF-,B activity as mice with p50/p52,/, T cells successfully rejected skin grafts. Rather, skin but not cardiac allografts effectively induced proliferation of graft-specific I,B,,N-Tg T cells. Rejection of skin grafts by I,B,,N-Tg mice was in part dependent on the presence of donor Langerhans cells (LC), a type of epidermal dendritic cells (DC), as lack of LC in donor skin grafts resulted in prolongation of skin allograft survival and injection of LC at the time of cardiac transplantation was sufficient to promote cardiac allograft rejection by I,B,,N-Tg mice. Our results suggest that LC allow NF-,B-impaired T cells to reach an activation threshold sufficient for transplant rejection. The combined blockade of T-cell-NF-,B with that of alternative pathways allowing activation of NF-,B-impaired T cells may be an effective strategy for tolerance induction to highly immunogenic organs. [source] Epidermal Langerhans cell migration and sensitisation to chemical allergensAPMIS, Issue 7-8 2003MARIE CUMBERBATCH Epidermal Langerhans cells (LC) form part of the wider family of dendritic cells (DC; professional antigen-processing and antigen-presenting cells). LC are considered to serve in the skin as sentinels of the adaptive immune system, surveying the local environment and transporting foreign antigen for presentation to responsive T lymphocytes in regional lymph nodes. As such, LC play pivotal roles in the initiation of cutaneous immune responses, including immune responses to chemical allergens encountered at skin surfaces. Here we explore two aspects of LC function in the context of sensitisation to chemical allergens. The first is consideration of the cytokine and chemokine signals that regulate and counter-regulate the mobilisation and migration of LC from the epidermis to skin-draining lymph nodes following topical sensitisation. The second is examination of the ways in which LC may influence the polarity of induced T lymphocytes, and thereby the quality of immune responses. [source] Expression of haptoglobin in human keratinocytes and Langerhans cellsBRITISH JOURNAL OF DERMATOLOGY, Issue 5 2005H. Wang Summary Background, Epidermal Langerhans cells (LCs) play an important role in cutaneous immunological reactions. Freshly obtained or intraepidermal LCs are incapable of activating autologous naive T cells. However, when they are cultured for 2,3 days, LCs are able to activate autologous T cells. It has been proposed that haptoglobin (Hp) is the inhibitor that prevents LC functional transformation in the skin. Abundant Hp has been found in the cytoplasm of epidermal LCs. However, the source of Hp in LCs has not been addressed. Objectives, To determine the expression of Hp in epidermal cells, and to provide evidence that there is a functional relationship between LCs and keratinocytes (KCs) through Hp. Methods, Normal human epidermal cells and HaCaT cells were used for detection of Hp mRNA by in situ hybridization and reverse transcription,polymerase chain reaction, and Hp protein by immunohistochemical staining, immunofluorescence counterstaining and Western blotting. Results, Hp mRNA was expressed in normal human KCs and HaCaT cells, but not in normal human epidermal LCs. Hp protein was detected by immunohistochemical staining and immunofluorescence counterstaining in CD1a+ epidermal dendritic cells (LCs), but not in KCs. Hp protein was weakly expressed by HaCaT cells. Conclusions, Hp mRNA is present in normal human KCs and HaCaT cells, suggesting that they have the potential to synthesize Hp protein. Normal human epidermal LCs are unable to synthesize Hp protein by themselves, although they have abundant Hp protein in their cytoplasm. It is likely that LCs acquire Hp through an exogenous pathway. [source] Prominent Langerhans' cell migration in the arthropod bite reactions simulating Langerhans' cell histiocytosisJOURNAL OF CUTANEOUS PATHOLOGY, Issue 12 2007Se Hoon Kim Background:, Epidermal Langerhans' cells (LCs) play pivotal roles in cutaneous immune responses. An encounter with antigens or other stimuli causes the mobilization and migration of LCs. Therefore, some dermatoses, which originated from antigenic stimuli or trauma, can show LC migration. Recently, we experienced several cases of anthropod bites that showed marked inflammatory infiltrates with eosinophils and CD1a-positive LCs. It was difficult to differentiate these cases from Langerhans' cell histiocytosis (LCH). Methods:, The degree and pattern of LC infiltration in the skin of arthropod bite reaction was evaluated. The characteristics of CD1a immunohistochemical expression in the arthropod bite reactions were compared with those of LCH. Results:, A few arthropod bite cases (approximately 36%) showed extensive CD1a-positive LCs in the dermis, especially in the perivascular area. In addition, the CD1a expression patterns of LCs in the arthropod bite reactions were dendritic, whereas that of tumor cells in LCH were distinctly membranous and cytoplasmic. Conclusion:, Some arthropod bite reactions can show marked CD1a-positive LCs in the dermis, especially in the perivascular area. The dendritic CD1a immunohistochemical staining pattern in arthropod bite reactions is useful in helping to differentiate from LCH. [source] TNF-, induces the generation of Langerin/(CD207)+ immature Langerhans-type dendritic cells from both CD14,CD1a, and CD14+CD1a, precursors derived from CD34+ cord blood cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2003Jean-François Arrighi Abstract CD34+ cell-derived hematopoietic precursors amplified with FLT3-ligand, thrombopoietin and stem cell factor became, after a 6-day induction with GM-CSF, IL-4 and TGF-,1, HLA-DR+, CD1a+, CD83,, CD86,, CD80, cells. A fraction of them expressed Langerin, Lag, and E-cadherin, resembling epidermal Langerhans cells (LC). TNF-, addedfor the last 3,days only marginally induced CD83 expression, but strikingly increased the proportion of immature Langerin+CD83, LC. Langerin+CD83+ and Langerin+CD83, cells were functionally distinct, the former internalizing less efficiently Langerin than the latter. Both CD1a,CD14, and CD1a,CD14+ cells sorted from FLT3-ligand, thrombopoietin and stem cell factor cultures responded to TNF-, by an increase of Langerin+ cells. Thus, TNF-, rescued LC precursors irrespective of their commitment to the monocytic lineage. When added to GM-CSF, IL-4 and TGF,,1 containing-cultures, LPS or IL-1, also induced significant numbers of Langerin+CD83, immature cells displaying a low allostimulatory activity, while CD40-ligand largely promoted highly allostimulatory Langerin,CD83+ cells. Altogether, these data show that in contrast to CD40-ligand, which induced LC maturation even in presence of TGF-,1, nonspecific proinflammatory factors such as TNF-,, IL-1, or LPS, essentially induced immature LC generation, and little cell activation in the presence of TGF-,1. [source] The human skin/chick chorioallantoic membrane model accurately predicts the potency of cosmetic allergensEXPERIMENTAL DERMATOLOGY, Issue 4 2009Dan Slodownik Abstract:, The current standard method for predicting contact allergenicity is the murine local lymph node assay (LLNA). Public objection to the use of animals in testing of cosmetics makes the development of a system that does not use sentient animals highly desirable. The chorioallantoic membrane (CAM) of the chick egg has been extensively used for the growth of normal and transformed mammalian tissues. The CAM is not innervated, and embryos are sacrificed before the development of pain perception. The aim of this study was to determine whether the sensitization phase of contact dermatitis to known cosmetic allergens can be quantified using CAM-engrafted human skin and how these results compare with published EC3 data obtained with the LLNA. We studied six common molecules used in allergen testing and quantified migration of epidermal Langerhans cells (LC) as a measure of their allergic potency. All agents with known allergic potential induced statistically significant migration of LC. The data obtained correlated well with published data for these allergens generated using the LLNA test. The human-skin CAM model therefore has great potential as an inexpensive, non-radioactive, in vivo alternative to the LLNA, which does not require the use of sentient animals. In addition, this system has the advantage of testing the allergic response of human, rather than animal skin. [source] A quantitative study of epidermal Langerhans cells in cutaneous leishmaniasis caused by Leishmania tropicaINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 11 2004Simin Meymandi MD Objective, The purpose of this study was to characterize the number and distribution of epidermal Langerhans cells in different clinical forms of dry-type cutaneous leishmaniasis (CL). Methods, Sixteen cases of dry-type cutaneous leishmaniasis caused by Leishmania tropica were studied. These cases were classified clinically as five cases of acute leishmaniasis with indurated papules, nodules and plaques with central crust formation and duration < 2 years, six cases of lupoid leishmaniasis with characteristic papules around previous scars of cutaneous leishmaniasis with duration > 2 years, and five cases of chronic nonlupoid type with nonhealing lesions of duration > 2 years. Paraffin-embedded blocks were stained with hematoxylin and eosin (H&E) and stained immunohistochemically for CD1a. Results, The number of Langerhans cells per millimeter length of epidermis was increased in acute cases compared to chronic and lupoid cases. Conclusions, Lesions of acute leishmaniasis contain the greatest amounts of antigen for presentation, so Langerhans cells increase in number and in trafficking to present antigens derived from Leishman bodies to the cellular immune system. In chronic leishmaniasis, the Langerhans cell population is reduced, perhaps because of exhaustion of the source of Langerhans cells, or because of reduced response to modified antigen. [source] Ultraviolet B radiation suppresses Langerhans cell migration in the dermis by down-regulation of ,4 integrinPHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE, Issue 3 2006Motoko Hamakawa Background/Purpose: Ultraviolet B (UVB) radiation affects the migration and function of epidermal Langerhans cells (LC) and causes immunosuppression of contact hypersensitivity. It is known that LC leaves the epidermis after exposure to UVB. To know the behavior of LC in the dermis after UVB radiation, we studied the effect of UVB radiation on the expression of integrin families on freshly isolated or cultured murine LC. We also examined whether UVB radiation affects the migration of LC to secondary lymphoid tissue chemokine (SLC/6Ckine). Methods: Integrin expressions of murine LC cultured in epidermal cell suspension were analyzed using flowcytometry. We used murine LC sorted flowcytometrically for binding assay to extracellular matrix and for migration assay to chemokine. Skin explant assay and immnohistochemical staining for ,cords formation' were performed as previously described. Results: Twenty and 40 mJ/cm2 of UVB radiation down-regulated the expression of ,4 integrin on 24 h-cultured LC, but not that of ,6, ,1, or ,4 integrin. The number of cultured LC adhered to fibronectin, a ligand for ,4 integrin, was decreased after UVB irradiation, while that to laminin, a ligand for ,6 integrin, was not influenced. UVB radiation reduced the number of migrating LC to SLC. Furthermore, skin sheet explant experiments showed that UVB radiation inhibited the ,cords' formation in dermal vessels of the 48 h-cultured skin. Conclusions: These data suggest that UVB radiation may suppress the migration of LC from the dermis to lymphatic vessels. UVB radiation may downregulate the adherence of LC to dermal fibronectin and migration to SLC, and consequently suppress the migration of LC from the UVB-irradiated dermis to lymphatics. [source] Immunophenotyping of inflammatory cells in lesional skin of the extrinsic and intrinsic types of atopic dermatitisBRITISH JOURNAL OF DERMATOLOGY, Issue 1 2004N-K. Rho Summary Background There is a subgroup of atopic dermatitis (AD) patients with normal total and specific IgE levels and negative skin tests towards common allergens. This form of the disease has been referred to as the ,intrinsic' form of AD. Although previous studies have demonstrated differences in the cytokine profile between the extrinsic and intrinsic subtypes, the pathogenesis of both subtypes of AD remains unclear. Objectives To compare the inflammatory micromilieu in both forms of AD. Methods Immunophenotyping of the inflammatory cells was performed in lesional and nonlesional skin from 18 patients with extrinsic and 17 with intrinsic AD. Results Immunohistochemical analysis revealed a high proportion of CD4+ T cells in the dermis, with a similar CD4/CD8 ratio in the two groups. The expression levels of other T-cell markers and epidermal Langerhans cells were increased in both forms of AD. Although the T-cell repertoires in the two subtypes were similar, dermal infiltration of eosinophils and eosinophil granular proteins was more prominent in the extrinsic type than in the intrinsic type. Eotaxin immunoreactivity was also significantly higher in the extrinsic subtype. Conclusions The data suggest that although the overall inflammatory microenvironment in the two subtypes appears to be similar, differences in T-cell cytokine production might contribute to the differential tissue eosinophilia in these subtypes. [source] Effect of PUVA, narrow-band UVB and cyclosporin on inflammatory cells of the psoriatic plaqueJOURNAL OF CUTANEOUS PATHOLOGY, Issue 3 2007Gul Erkin Background:, Because antigen presenting is necessary for T-cell activation, antigen-presenting cells should be involved in the pathogenesis of psoriasis. In this study, our purpose was to evaluate and compare effects of PUVA, cyclosporine A and narrow-band UVB on dendritic cells and activated lymphocytes in the psoriatic lesions. Methods:, Forty-five volunteered patients (15 patients in each treatment group as PUVA, cyclosporin A and narrow-band UVB) were enrolled in this study. Lesional skin biopsies were taken from each patient before and after treatments. Fresh frozen biopsies were studied for the expressions of CD1a, CD68, CD86, CD4, CD8 and HLA-DR proteins by immunohistochemistry. Results:, There was no correlation between severity of the lesions and expressions of the antigens. Only PUVA significantly decreased CD1a+ epidermal Langerhans cells' (LCs) counts. Treatment modalities decreased expression of costimulator CD86, and most of them decrease antigen-presenting capacity of skin by decreasing HLA class-II expression. Conclusions:, All treatment modalities equally reduce lymphocytes, macrophages and dendritic cells. PUVA is the only treatment that decreases epidermal LCs. All treatments effectively diminish expression of CD86 and inhibit this step of inflammation. [source] CD4 is expressed by epidermal Langerhans' cells predominantly as covalent dimersEXPERIMENTAL DERMATOLOGY, Issue 5 2003G. W. Lynch Abstract:, Langerhans' cells (LC) of skin are CD4 expressing, dendritic, antigen-presenting cells, that are essential for activation of primary immune responses and are productively infected by HIV. We have shown previously that lymphocytes and monocytes express CD4 both as monomers and covalently linked homodimers. In those cells the 55-kDa monomer structure predominates. LC in un-fractionated human epidermal cell (EC) suspension also expresses both forms of CD4, but in EC the dimer form is predominant. Because isolation of LC into single cell suspension by trypsin, as is routinely used for LC isolation, degrades CD4, a systematic study for an alternate procedure for LC isolation was performed. Thus it was found that collagenase blend F treatment can efficiently release LC into suspension, under conditions of only minimal degradation of control soluble recombinant CD4 or CEM-T4 or THP-1 cell CD4, or importantly of LC surface CD4. SDS,PAGE immunoblotting of purified LC extracted from EC by collagenase confirmed CD4 structure as predominantly 110-kDa dimers, with only minimal 55-kDa monomers. The suitability of LC prepared thus for functional studies was demonstrated with binding of functional ligand HIV gp120. It remains to be determined, however, why tissue embedded LC express mainly CD4 dimers, but single-celled blood lymphocytes and monocytes mainly monomers. [source] | ||||||||||||||||||||||