Immunocytochemical detection of the carbohydrate antigen, Sialyl Lewisx, in normal human skin and during irritant contact dermatitis

Abstract Sialys Lewis^x (SLex) is a ligand for the E-selectin and the interaction of E-selectin on the endothelium and SLe^x on T cells may be important for T-cell migration into the skin. We investigated the expression of SLe^x on Langerhans cells (LC) in normal skin and on LC repopulating epidermis deprived of LC due to a preceding irritant contact dermatitis. SLe^x was visualized by fluorescence and light microscopic immunocytochemistry using the monoclonal antibody. CSLEX-1. The results showed that about 40% of LC in normal epidermis express SLe^x. In the repopulation phase, most of the epidermal cells were CDla⁺/SLe^x+. We suggest that SLe^x is present on epidermal LC that have recently immigrated from the dermis.     

Characterization of cutaneous antigen presentation in partially inbred miniature swine

Abstract MHC class I and II-defined, partially inbred miniature swine have recently become available as a large animal model in transplantation immunology. To investigate cutaneous immunocompetence in this model, cutaneous antigen presenting cell (ARC) function was assessed. For morphologic analysis, punch biopsies were examined by electron microscopy. By this technique, epidermal Langerhans cells bearing typical Birbeck granules could be detected. For functional studies, epidermal cell (EC) suspensions were prepared from split thickness skin specimens. Using FACS analysis, freshly prepared epidermal cell suspensions contained 1.8-4.7% MHC class II-positive cells. These EC potently stimulated allogeneic nylon wool-enriched peripheral blood T cells in the primary mixed EC-lymphocyte reaction. For in vivo assessment of cutaneous APC function. EC suspensions enriched for or depleted of class II-positive EC were generated by panning of class II-positive EC using mouse anti-MHC class II antibodies and anti-mouse IgG-coatcd petri dishes. EC were then coupled to the hapten trinitrophenol (TNP) and injected s.c. into autologous or MHC-mismatched pigs twice at a one week interval. One week later, pigs were challenged by s.c.-injection of 0.5-1 × 10⁷ TNP-coupled or uncoupled EC. Autologous unseparated EC as well as EC enriched for MHC class II-positive cells were able to sensitize naive animals against TNP, whereas neither TNP-coupled EC depleted of class II-positive APC, MHC-mismatched EC coupled to TNP, nor uncoupled EC induced immunity to TNP. Our data indicate that inbred miniature swine possess competent cutaneous APC which are able to induce cutaneous immunity in a manner similar to Langerhans cells in murine or human skin.     

Precursors of Langerhans cells

LC are dendritic cells localized in the supra-basal layer of the epidermis and in mucous epithelia. Their density ranges from 200 to 900 cells/mm². Their first function is to take an antigen, process it and present the processed antigen to the lymphocytes ([1] Misery L. La cellule de Langerhans. Editions Techniques, Encycl. Méd. Chir. Dermatologie 1994;12-220-B-10). They are involved in numerous diseases. The origin of these cells has been debated but a consensus has now been reached. Langerhans cells (LC) were first described in 1868 by Paul Langerhans ([2] Über die Nerven der menschlichen Haut. Virch Arch A (Pathol Anat) 1868;44:325–337). He thought that it was a nerve cell. LC were first considered to be a component of the nervous system because their dendritic processes are similar so nerve fibers and because of their staining by gold chloride. Other authors have discussed a possible relationship with melanocytes. LC were regarded either as melanocytes, the progeny of melanocytes after division, or as melanocytes in an arrested stage of development ([3] Masson P. My conception of cellular naevi. Cancer 1951;4:9–15; [4] Fan J, Schoenfeld RJ, Hunter J. A study of the epidermal clear cells with special reference to their relationship to the cells of Langerhans. J Invest Dermatol 1959;32:445–450; [5] Zelickson AS. Granule formation in the Langerhans cell. J Invest Dermatol 1966;47:498–502). S100 protein is expressed on melanocytes, on nerve cells and on LC ([6] Cocchia D, Michetti F, Donato R. Immunochemical and immunocytochemical localization of S100 antigen in normal human skin. Nature 1981;294:85–87), but this does not imply that there is a common lineage. Subsequent research showed that this cell is in fact an immune cell. Electron microscopy has given us a new and very important insight into the nature of LC. Thus, there is no tonofilament, no desmosome and no melanosome ([7] Birbeck MS, Breathnach AS, Everall JD. An electron microscopy study of basal melanocyte and high level clear cell (Langerhans cell) in vitiligo. J Invest Dermatol 1961;37:51–63). The most important ultrastructural feature is the presence of Birbeck granules. Many experiments have pointed to a hone-marrow origin of LC and their probable relationship with the phagocytic mononuclear cell system.     

Comparative analysis of CD80 and CD86 on human Langerhans cells: expression and function

Abstract Although both CD80 (B7–1) and CD86 (B7–2/B70) have been recently identified in cultured human Langerhans cells (LC), little is known of the role and regulatory properties of CD80 and CD86 on human LC. We present here the results of a study comparing the expression and function of CD80 and CD86 in human LC using the T-helper type-1 cytokines IL-2 and interferon γ (IFN)-γ, and the T-helper type-2 cytokines IL-10, IL-4 and granulocyte/macrophage colony-stimulating factor (GM-CSF). Freshly isolated human LC expressed little CD80 and CD86 in vitro, but the expression of both molecules was rapidly induced during a 72-h incubation with cytokines and the expression of CD86 occurred much earlier and more strongly than that of CD80. The expression of both CD80 and CD86 was upregulated by GM-CSF and downregulated by IL-10, and the expression of CD86, but not that of CD80, was upregulated by both IL-4 and IFN-γ. Finally, pretreatment of LC with GM-CSF and IFN-γ, but not with IL-4, enhanced the alloreactive T-cell proliferation induced by the LC, and IL-10 pretreatment of LC decreased their capacity for alloreaction. These results indicate that the expression of both CD80 and CD86 on human LC may be regulated by these cytokines (IL-2, IL-4, GM-CSF, IFN-γ and IL-10) secreted from helper T cells infiltrating into the inflammatory microenvironment. Received: 4 December 1997     

The effect of physical training on insulin secretion of rat pancreatic islets

Rats were either physically trained by a 12-wk swimming program or were freely eating or weight matched, sedentary controls. Islets of Langerhans were isolated and incubated at various glucose concentrations. Within the range of physiological glucose concentrations the rate of insulin release from islets of trained rats was lower than that from islets of sedentary controls. The DNA content of the islets was similar in the different groups. The demonstrated decreased glucose sensitivity of the insulin secretory mechanism within the β-cells of trained rats may partly explain the finding of lower plasma insulin concentrations during intravenous glucose tolerance test in these rats compared with sedentary rats. Epididymal fat pads of trained rats were smaller than those of weight matched controls which in turn were smaller than those of freely eating controls, these differences being due to differences in fat cell size. The lower glucose sensitivity of the β-cells in trained rats was probably not a consequence of the low body weight and small fat depots in these rats.     

Zur Kinetik der Langerhans-Zellen der Epidermis

Zusammenfassung Die Zellen des Stratum spinosum befinden sich in ständiger ungerichteter Bewegung und können in ihrer Geschwindigkeit als einer Maxwellschen Verteilung folgend gedacht werden. Die Langerhans-Zellen nehmen an dieser ungerichteten Bewegung teil, treffen jedoch wegen ihrer Dendritenform auf einen viel höheren Strömungswiderstand. Auf Grund eines Gedankenmodelles wird ihre wahrscheinlichste Geschwindigkeit als die Hälfte der der Keratinocyten errechnet. Als Konsequenz ergibt sich eine doppelt so lange Transitzeit sowie eine halb so große Mitoserate und Abstoßungsrate ins Stratum corneum wie bei der Keratinocytenpopulation. Die Langerhans-Zellen müssen schließlich auf die Keratinocyten wie Bewegungshomogenisatoren wirken.

---

     

Uncommon histiocytic disorders: the non-Langerhans cell histiocytoses

BACKGROUND: Histiocytic disorders are currently identified by their component cells. The non-Langerhans Cell Histiocytoses (non-LCH) are a group of disorders defined by the accumulation of histiocytes that do not meet the phenotypic criteria for the diagnosis of Langerhans cells (LCs). The non-LCH consist of a long list of diverse disorders which have been difficult to categorize. A conceptual way to think of these disorders that make them less confusing and easier to remember is proposed based on immunophenotyping and clinical presentation. RESULTS: Clinically the non-LCH can be divided into 3 groups, those that predominantly affect skin, those that affect skin but have a major systemic component, and those that primarily involve extracutaneous sites, although skin may be involved. Immunohistochernically many of the non-LCH appear to arise from the same precursor cell namely the dermal dendrocyte. Juvenile Xanthogranuloma (JXG) is the model of the dermal dendrocyte-derived non-LCH. Other non-LCH with differing clinical presentation and occurring at different ages but with an identical immunophenotype appear to form a spectrum of the same disorder, deriving from the same precursor cell at different stages of maturation. They should be considered as members of a JXG family. Non-JXG family members include Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease). CONCLUSION: The non-LCH can be classified as JXG family and non-JXG family and subdivided according to fairly clear-cut clinical criteria. Utilization of this type of approach will allow better categorization, easier review of the literature and more accurate therapy decision-making.     

Langerin (CD207) Staining in Normal Pediatric Tissues,Reactive Lymph Nodes,and Childhood Histiocytic Disorders

Langerin is a recently identified lectin for which antibodies can be used as immunohistochemical markers of Langerhans cells (LCs). We describe the distribution of staining in autopsy pediatric tissues, dermatopathic and other reactive lymph nodes, and childhood histiocytic lesions using the 12D6 antibody (Novocastra). We also correlate CD1a (antibody O1O) staining to these factors. Langerin on epidermal LCs has a coarsely granular cell membrane and a cytoplasmic staining pattern that is always associated with CD1a expression. All 6 skin samples had Langerin⁺/CD1a⁺ LCs within the epidermis. Six of 8 thymuses showed single scattered dendritic-shaped cells in the medulla and rare cells within Hassall corpuscles that coexpressed Langerin and CD1a. Cortical thymocytes were CD1a⁺/Langerin^–. Four of 8 livers examined showed a sinusoidal lining pattern of Langerin+/CD1a^–. All 15 autopsy lymph nodes showed a similarly strong Langerin⁺/CD1a^– sinus pattern of staining on fixed tissue elements, mostly in medullary sinuses. All 12 dermatopathic lymph nodes showed accumulation of Langerin⁺/CD1a⁺ cells in the pale paracortical nodules. All 24 instances of LC histiocytosis (LCH) were Langerin⁺/CD1a⁺. All 12 non-LCH histiocytic disorders are negative for Langerin in the histiocytes of interest. We conclude that Langerin is coexpressed with CD1a on LCs and LCH. Lymph node sinuses and hepatic sinusoids show Langerin⁺/CD1a^– cells, indicating that, when used alone to confirm LCH infiltration, the 12D6 antibody should be used with caution. At other sites, its diagnostic accuracy is similar to that of CD1a.     

Liver Involvement in the Histiocytic Disorders of Childhood

The liver can be involved directly, by infiltration, and indirectly—by remote effects—in the histiocytoses of childhood. Langerhans cell disease, the most well recognized of these, infiltrates the liver directly but has a remarkable selectivity for the bile ducts. Early involvement is by Langerhans cell histiocytosis (LCH) infiltration leading to a sclerosing cholangitis and, eventually, biliary cirrhosis. Gamma glutamyl transpeptidase is a sensitive indicator of liver infiltration in a child with LCH. The indirect effects on the liver of LCH elsewhere in the body are mediated through an accompanying macrophage activation syndrome that is most likely responsible for hepatomegaly and hypoalbuminemia but without direct infiltration. These indirect effects are completely reversible. Juvenile xanthogranuloma/xanthoma disseminatum, a related dendritic cell disorder that can have systemic manifestations, has a strikingly different pattern, with a predominantly portal infiltrate spilling over into the adjacent lobule but sparing the biliary tree. The biology of the liver lesions is not clear but regression has been documented. Myeloproliferative disorders and myeloid leukemias can express CD1a and/or S100 protein, mimicking LCH but distinguished by their sinusoidal pattern. The primary macrophage histiocytoses such as the familial hemophagocytic syndromes can lead to severe liver damage. Although a portal lymphohistiocytic infiltrate is most characteristic, it is probably cytokine-mediated hepatocellular damage that can cause substantial functional impairment or even hepatic failure as a presenting feature. Liver involvement in other, more unusual histiocytic disorders, is also illustrated.