A Model System Using Tape Stripping for Characterization of Langerhans Cell-Precursors In Vivo

Holzmann, Sandra; Tripp, Christoph H.; Schmuth, Matthias; Janke, Katrin; Koch, Franz; Saeland, Sem; Stoitzner, Patrizia; Romani, Nikolaus

doi:10.1111/j.0022-202x.2004.22520.x

Cited by 74 publications

(73 citation statements)

References 45 publications

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“…We did not use tape stripping, which may disturb the integrity of the epidermis (20). Even without the addition of adjuvants, application of cream under an occlusive bandage caused m-LCs to up-regulate both CD80 and CD86, producing a bimodal CD80/ 86 profile as m-LCs first reached the dLN 48 h after immunization ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Langerhans cells are precommitted to immune tolerance induction

Shklovskaya¹,

O’Sullivan

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

151

135

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Antigen-dependent interactions between T lymphocytes and dendritic cells (DCs) can produce two distinct outcomes: tolerance and immunity. It is generally considered that all DC subsets are capable of supporting both tolerogenic and immunogenic responses, depending on their exposure to activating signals. Here, we tested whether epidermal Langerhans cells (LCs) can support immunogenic responses in vivo in the absence of antigen presentation by other DC subsets. CD4 T cells responding to antigen presentation by activated LCs initially proliferated but then failed to differentiate into effector/memory cells or to survive long term. The tolerogenic function of LCs was maintained after exposure to potent adjuvants and occurred despite up-regulation of the costimulatory molecules CD80, CD86, and IL-12, but was consistent with their failure to translocate the NF-κB family member RelB from the cytoplasm to the nucleus. Commitment of LCs to tolerogenic function may explain why commensal microorganisms expressing Toll-like receptor (TLR) ligands but confined to the skin epithelium are tolerated, whereas invading pathogens that breach the epithelial basement membrane and activate dermal DCs stimulate a strong immune response.D endritic cells (DCs) initiate adaptive immune responses by priming antigen-specific T cells in secondary lymphoid organs. After sampling antigens in peripheral tissues, DCs migrate to lymph nodes (LN), where they present antigenic peptides bound to major histocompatibility (MHC) molecules (1). Epidermal Langerhans cells (LCs) have long been regarded as prototypic DCs, highly active in antigen uptake and rapidly acquiring potent costimulatory capacity after in vitro culture (2). Recently, the immunogenicity of LCs has been questioned on the basis of findings in several in vivo experimental models. During herpes viral infection of the skin, migrated LCs isolated from draining LN (dLN) were unable to induce proliferation of virusspecific CD8 T cells in vitro (3). In LC ablation models, positive (4, 5), negative (6-8), and redundant (9) contributions of LCs to contact hypersensitivity responses were reported. The current lack of consensus regarding LC function may relate, at least in part, to the difficulties in determining the contribution of a relatively small number of LCs to responses driven primarily by non-LC DC subsets in cutaneous LN (cLN).Here we directly tested the in vivo function of LCs, using a previously described bone marrow (BM) chimeric mouse model in which only LCs can present specific antigen to CD4 T cells (10). In this model, all DC subsets express MHC class II IA molecules but only LCs express MHC class II IE, which is absolutely required to present moth cytochrome C peptide (pMCC) to 5C.C7 T-cell receptor (TCR) transgenic T cells (11,12). The response of adoptively transferred 5C.C7 CD4 T cells can thus be used as a readout for LC function. We compared 5C.C7 T-cell responses to LCs with those in chimeras expressing IE on nonepidermal DCs or all DC subsets, immunizing with peptide o...

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Section: Resultsmentioning

confidence: 99%

Langerhans cells are precommitted to immune tolerance induction

Shklovskaya¹,

O’Sullivan

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

151

135

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“…Disturbing the skin barrier by tape stripping (7), or by simultaneous application of cholera toxin (6) or TLR ligands such as CpG oligonucleotides (6) or imiquimod (25) have all been shown to provide an adjuvant effect. We chose to use skin barrier disruption because this method might be applicable in clinical trials, and because we had observed that it effectively induced migration of LC from the skin to the draining lymph nodes (26). Throughout our study, we compared groups of mice that received OVA on untreated or on tape-stripped skin.…”

Section: Discussionmentioning

confidence: 99%

Tumor Immunotherapy by Epicutaneous Immunization Requires Langerhans Cells

Stoitzner

Green

Jung

et al. 2008

The Journal of Immunology

Self Cite

103

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A role for Langerhans cells (LC) in the induction of immune responses in the skin has yet to be conclusively demonstrated. We used skin immunization with OVA protein to induce immune responses against OVA-expressing melanoma cells. Mice injected with OVA-specific CD8+ T cells and immunized with OVA onto barrier-disrupted skin had increased numbers of CD8+ T cells in the blood that produced IFN-γ and killed target cells. These mice generated accelerated cytotoxic responses after secondary immunization with OVA. Prophylactic or therapeutic immunization with OVA onto barrier-disrupted skin inhibited the growth of B16.OVA tumors. LC played a critical role in the immunization process because depletion of LC at the time of skin immunization dramatically reduced the tumor-protective effect. The topically applied Ag was presented by skin-derived LC in draining lymph nodes to CD8+ T cells. Thus, targeting of tumor Ags to LC in vivo is an effective strategy for tumor immunotherapy.

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“…8A). It has been reported that LCs can be replaced from precursors that originate in the blood, such as those of monocyte origin (17,28). In addition, LC precursors also exist within the skin itself (15).…”

Section: On Resolution Of Infection Lc Replacement In the Reformed Ementioning

confidence: 99%

Differential Migration of Epidermal and Dermal Dendritic Cells during Skin Infection

Eidsmo

Allan

Caminschi

et al. 2009

The Journal of Immunology

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Dendritic cells (DCs) are extremely heterogeneous, most evident in the skin where a variety of different subsets have been identified in recent years. DCs of healthy skin include a number of distinct populations in the dermal layer as well as the well-characterized Langerhans cells (LCs) of the epidermis. These steady-state populations are augmented during bouts of local inflammation by additional monocyte-derived DCs. In an effort to better understand the distinction between the different subsets, we examined their behavior following skin infection with HSV. LC emigration rapidly followed appearance of virus in the skin and resulted in depopulation of regions in areas surrounding infected nerve endings. A separate DC population was found to accumulate within the dermis under patches of active epidermal infection with at least some derived from blood monocyte precursors. Ag-positive DCs could occasionally be found in these dermal accumulations, although they represented a minority of DCs in these areas. In addition, infected DCs appeared compromised in their trafficking capabilities and were largely absent from the migrating population. On resolution of skin disease, LCs repopulated the reformed epidermis and these were of mixed origin, with around half entering from the circulation and the remainder derived from local progenitors. Overall, our results show a range of migrational complexities between distinct skin DC populations as a consequence of localized infection.

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A Model System Using Tape Stripping for Characterization of Langerhans Cell-Precursors In Vivo

Cited by 74 publications

References 45 publications

Langerhans cells are precommitted to immune tolerance induction

Langerhans cells are precommitted to immune tolerance induction

Tumor Immunotherapy by Epicutaneous Immunization Requires Langerhans Cells

Differential Migration of Epidermal and Dermal Dendritic Cells during Skin Infection

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