A Monoclonal Antibody Specifically Reactive to Human Langerhans Cells

Kashihara, M; Ueda, Masamichi; Horiguchi, Yuji; Furukawa, Fukumi; Hanaoka, Masao; Imamura, Sadao

doi:10.1111/1523-1747.ep12455849

Cited by 148 publications

(76 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…From day 4 on, loosely adherent aggregates of cells appeared in culture, which increased in size and number with time. At day 7, presumptive LCs were found only in multicellular clusters, as indicated by staining with CD1a and with the unique LC marker Lag (18) (Fig. 2, A-D).…”

Section: Resultsmentioning

confidence: 95%

Large-Scale Culture and Selective Maturation of Human Langerhans Cells from Granulocyte Colony-Stimulating Factor-Mobilized CD34+ Progenitors

Gatti

Velleca

Biedermann³

et al. 2000

The Journal of Immunology

111

View full text Add to dashboard Cite

Dendritic cells (DCs) play a critical role as APCs in the induction of the primary immune response. Their capacity for Ag processing and presentation is tightly regulated, controlled by a terminal developmental sequence accompanied by striking changes in morphology, organization, and function. The maturation process, which converts DCs from cells adapted for Ag accumulation to cells adapted for T cell stimulation, remains poorly understood due in part to difficulties in the culture and manipulation of DCs of defined lineages. To address these issues, we have devised conditions for the culture of a single DC type, Langerhans cells (LCs), using CD34+ cells from G-CSF-mobilized patients. Homogenous populations of LCs, replete with abundant immunocytochemically demonstrable Birbeck granules, could be stably maintained as immature DCs for long periods in culture. Unlike other human DC preparations, the LCs remained fully differentiated after cytokine removal. Following exposure to TNF-α, LPS, or CD40 ligand, the LCs could be synchronously induced to mature. Depending on the agent used, distinct types of LCs emerged differing in their capacity for T cell stimulation, IL-12 production, intracellular localization of MHC products, and overall morphology. Most interestingly, the expression of different sets of Toll family receptors is induced or down-regulated according to the maturation stimulus provided. These results strongly suggest that different proinflammatory stimuli might drive distinct developmental events.

show abstract

Section: Resultsmentioning

confidence: 95%

Large-Scale Culture and Selective Maturation of Human Langerhans Cells from Granulocyte Colony-Stimulating Factor-Mobilized CD34+ Progenitors

Gatti

Velleca

Biedermann³

et al. 2000

The Journal of Immunology

111

View full text Add to dashboard Cite

show abstract

“…Mouse monoclonal antibodies (mAbs) were as follows: anti-lag (IgG1, recognizing an intracellular epitope of Langerin; kindly provided by Dr. Sadao Imamura, Kyoto University, Sakyo-ku, Kyoto, Japan) (Kashihara et al, 1986;Valladeau et al, 2000), DCGM4 (IgG1, recognizing an extracellular epitope of Langerin; Immunotech, Marseille, France) (Valladeau et al, 1999), L243 (IgG2a, anti-DR␣␤ dimmers; BD Biosciences, San Jose, CA), fluorescein isothiocyanate (FITC)-conjugated H1149 (IgG1, anti-CD1a; BD PharMingen, San Diego, CA), H5C6 (IgG1, anti-CD63; kindly provided by Dr. François Lanza, EFS-Alsace, Strasbourg), tetramethylrhodamine B isothiocyanate (TRITC)-conjugated Phalloidin (Sigma, St. Louis, MO), and H4B4 (IgG1, anti-Lamp-2 [CD107b], BD PharMingen). Rabbit anti-EEA1 antiserum (Simonsen et al, 1998) was a generous gift of Dr. Harald Steinmark, (EMBL, Heidelberg, Germany).…”

Section: Antibodies and Reagentsmentioning

confidence: 99%

Birbeck Granules Are Subdomains of Endosomal Recycling Compartment in Human Epidermal Langerhans Cells, Which Form Where Langerin Accumulates

Dermott

Ziylan

Spehner

et al. 2002

MBoC

166

155

View full text Add to dashboard Cite

Birbeck granules are unusual rod-shaped structures specific to epidermal Langerhans cells, whose origin and function remain undetermined. We investigated the intracellular location and fate of Langerin, a protein implicated in Birbeck granule biogenesis, in human epidermal Langerhans cells. In the steady state, Langerin is predominantly found in the endosomal recycling compartment and in Birbeck granules. Langerin internalizes by classical receptor-mediated endocytosis and the first Birbeck granules accessible to endocytosed Langerin are those connected to recycling endosomes in the pericentriolar area, where Langerin accumulates. Drug-induced inhibition of endocytosis results in the appearance of abundant open-ended Birbeck granule-like structures appended to the plasma membrane, whereas inhibition of recycling induces Birbeck granules to merge with a tubular endosomal network. In mature Langerhans cells, Langerin traffic is abolished and the loss of internal Langerin is associated with a concomitant depletion of Birbeck granules. Our results demonstrate an exchange of Langerin between early endosomal compartments and the plasma membrane, with dynamic retention in the endosomal recycling compartment. They show that Birbeck granules are not endocytotic structures, rather they are subdomains of the endosomal recycling compartment that form where Langerin accumulates. Finally, our results implicate ADP-ribosylation factor proteins in Langerin trafficking and the exchange between Birbeck granules and other endosomal membranes. INTRODUCTIONLangerhans cells (LCs), the representatives of the dendritic cell lineage in the epidermis and mucosal tissues, capture antigen in the skin before migrating to the T-cell-dependent areas of draining lymph nodes. During this migration, they undergo a maturation process that allows them to present antigens to naive T cells (Kripke et al., 1990;Moll et al., 1993). Notably, Langerhans cells are the only epidermal cells to constitutively express major histocompatibility complex class II molecules (Klareskog et al., 1977;Rowden et al., 1977), CD1a molecules (Fithian et al., 1981), and Langerin (Valladeau et al., 2000) at their cell surface. In addition, Langerhans cells differ ultrastructurally from other dendritic cells through the presence of Birbeck granules (BGs), distinctive rod-shaped structures of variable length with a central, periodically striated lamella (Birbeck et al., 1961).Despite the use of "dynamic" electron microscope studies (reviewed in Schuler et al., 1991), Birbeck granules remain enigmatic. Specifically, conflicting theories exist regarding Article published online ahead of print. Mol. Biol. Cell 10.1091/ mbc.01-06-0300. Article and publication date are at www.molbiolcell.org/cgi/doi/10.1091/mbc.01-06-0300.† These authors contributed equally to this work and are listed in alphabetical order. # Corresponding author. E-mail address: daniel.hanau@efs-alsace.fr. Abbreviations used: Au, gold-labeled; BG, Birbeck granule; ERC, endosomal recycling compartment; Fi, freshl...

show abstract

“…We evaluated the density of immature LC expressing CD1a and LAG (a protein associated with Birbeck granules 22 ) in paired biopsies derived from the exocervix and TZ or the exocervix and SILs of individual patients. Figure 1 shows the results of our analysis of the density of CD1a and LAG positive cells in the TZ and SILs in comparison to the paired exocervix.…”

Section: Langerhans Cell Densitymentioning

confidence: 99%

Influence of the mucosal epithelium microenvironment on Langerhans cells: Implications for the development of squamous intraepithelial lesions of the cervix

Giannini

Hubert

Doyen

et al. 2001

Intl Journal of Cancer

101

View full text Add to dashboard Cite

We have addressed the notion that the initiation and progression of human papillomavirus associated cancer of the uterine cervix are associated with alterations of Langerhans cells (LC) within the mucosal squamous epithelium. Since the transformation zone (TZ) of the cervix is the site where the majority of squamous intraepithelial lesions (SIL) are initiated, in contrast to the exocervix, we decided to investigate the influence of the local microenvironment within the TZ on the function and density of LC. We show that the TZ is associated with a significant reduction in the density of immature LC (CD1a/LAG) compared to the exocervix. In contrast, the development of SILs is attributed with a relative increased density of immature LC, compared to the TZ. Furthermore, we show that this variability in LC density is correlated with a differential expression of TNF␣ and MIP3␣ within the micro-environment of the TZ and SILs. Both TZ and SIL epithelium-derived LC, in the presence of allogeneic PBMC, induced lower levels of proliferation and IL2 production and higher levels of the immunosuppressive cytokine IL10 in comparison to the exocervix. Nevertheless, the epithelium-derived LC in SILs exhibits a reduction in their functional activity, relative to the TZ. Together our studies suggest that the immunosurveillance within the epithelium of the TZ may be intrinsically perturbed due to the altered expression of chemokines/cytokines and the concomitant diminished density of LC. Furthermore, following HPV infection and the development of SILs, the function of LC may be further incapacitated by viral associated mechanisms. © 2002 Wiley-Liss, Inc. Key words: Langerhans cells (LC); transformation zone (TZ); squamous intraepithelial lesions (SILs); human papillomavirus (HPV); local immunityThe chronic infection of keratinocytes of the uterine cervix by the human papillomavirus (HPV) is associated with the development of cervical cancer. Despite the evidence that HPV is strongly implicated as the causative agent in the etiology of cervical cancer and its precursors (SIL, squamous intraepithelial lesion), HPV infection alone is not sufficient for cancer development. 1 The role of the intrinsic immunity in controlling HPV infection and the subsequent development of SILs is shown indirectly by the increased frequency of HPV-associated lesions in patients with depressed cell-mediated immunity. 2,3 For the most part, the development of SIL and/or cervical cancer is preferentially associated with a local type II (IL4/IL6) and/or immunosuppressive (IL 10) cytokine pattern, 4 -7 not a cell-mediated type I immune response, which is more appropriate for tumor immunity. Given that immune responses in mucosal sites are frequently dominated by a "default" type 2 response, 8,9 it is essential to consider mechanisms that contribute to this predisposition in order to design vaccine strategies to promote a localized cell-mediated immunity.The squamous epithelium of the cervix is composed mainly of keratinocytes, the primary target of HPV and a ...

show abstract

A Monoclonal Antibody Specifically Reactive to Human Langerhans Cells

Cited by 148 publications

References 38 publications

Large-Scale Culture and Selective Maturation of Human Langerhans Cells from Granulocyte Colony-Stimulating Factor-Mobilized CD34+ Progenitors

Large-Scale Culture and Selective Maturation of Human Langerhans Cells from Granulocyte Colony-Stimulating Factor-Mobilized CD34+ Progenitors

Birbeck Granules Are Subdomains of Endosomal Recycling Compartment in Human Epidermal Langerhans Cells, Which Form Where Langerin Accumulates

Influence of the mucosal epithelium microenvironment on Langerhans cells: Implications for the development of squamous intraepithelial lesions of the cervix

Contact Info

Product

Resources

About