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HLA-Ig Based Artificial Antigen Presenting Cells for Efficient ex vivo Expansion of Human CTL
Published on: April 11, 2011
Langerhans cells cross-present antigen derived from skin
Patrizia Stoitzner1, Christoph H Tripp, Andreas Eberhart
1Department of Dermatology, Innsbruck Medical University, 6020 Innsbruck, Austria.
Insights
Langerhans cells (LCs) in the skin can cross-present external antigens to CD8+ T cells, triggering immune responses. This finding is significant for developing epicutaneous vaccination strategies.
Area of Science:
- Immunology
- Dermatology
- Cell Biology
Background:
- Dendritic cells (DCs) are known for cross-presentation of exogenous antigens on MHC class I to CD8+ T cells.
- Langerhans cells (LCs), the primary DCs in the epidermis, have poorly understood cross-presentation capabilities.
Purpose of the Study:
- To investigate the capacity of murine Langerhans cells (LCs) to cross-present exogenous antigens.
- To determine the functional consequences of LC-mediated cross-presentation on CD8+ T cells.
- To assess the potential role of LCs in epicutaneous vaccination.
Main Methods:
- Isolation and in vitro culture of murine LCs.
- Assessment of antigen cross-presentation using ovalbumin protein and peptide.
- Utilizing transporter associated with antigen processing (TAP)-1-deficient mice.
- In vivo studies involving epicutaneous antigen application and T cell proliferation assays.
Main Results:
- Isolated LCs demonstrated cross-presentation of soluble and cell-associated ovalbumin on MHC class I to CD8+ T cells.
- Cross-presentation by LCs was less potent than spleen-derived CD8+ DCs but involved a TAP-dependent pathway.
- Migratory LCs ingested epidermal antigens and presented them to T cells.
- LC cross-presentation induced IFN-gamma production and cytotoxicity in antigen-specific CD8+ T cells.
- Epicutaneous ovalbumin application led to in vivo OT-I T cell proliferation, enhanced by skin inflammation.
Conclusions:
- Langerhans cells are capable of cross-presenting exogenous antigens to CD8+ T cells, inducing effector functions.
- LCs contribute to immune surveillance in the skin and may play a crucial role in epicutaneous vaccination.
Abstract:
Dendritic cells (DC) efficiently cross-present exogenous antigen on MHC class I molecules to CD8+ T cells. However, little is known about cross-presentation by Langerhans cells (LC), the DCs of the epidermis. Therefore, we investigated this issue in detail. Isolated murine LCs were able to cross-present soluble ovalbumin protein on MHC-class I molecules to antigen-specific CD8+ T cells, albeit less potently than the CD8+ DC subsets from spleen. Furthermore, LCs cross-presented cell-associated ovalbumin peptide and protein expressed by neighboring keratinocytes. Use of transporter associated with antigen processing (TAP-1)-deficient mice suggested a TAP-dependent pathway. Similar observations were made with migratory LC. Antigen expressed in the epidermis was ingested by LCs during migration from the epidermis and presented to antigen-specific T cells in vitro. Cross-presentation of ovalbumin protein by LCs induced IFN-gamma production and cytotoxicity in antigen-specific CD8+ T cells. Additionally, epicutaneous application of ovalbumin protein induced in vivo proliferation of OT-I T cells in the draining lymph nodes; this was markedly enhanced when antigen was applied to inflamed, barrier-disrupted skin. Thus, LCs cross-present exogenous antigen to CD8+ T cells and induce effector functions, like cytokine production and cytotoxicity, and may thereby critically contribute in epicutaneous vaccination approaches.
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