Reifung und Migration von Langerhanszellen nach Stimulation durch liposomale Antigene - ein murines Modell zur transcutanen Tumorvaccinierung

In den letzten Jahren hat die Wissenschaft zahlreiche neue Erkenntnisse zur transcutanen Tumorvaccinierung gewonnen. Die Langerhanszellen nehmen dabei als Dendritische Zellen der Epidermis eine zentrale Rolle bei der Kontrolle des Immunsystems ein [Romani et al., 2001]. Dendritische Zellen haben...

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Bibliographic Details
Main Author: Harbrecht, Jan Christoph
Contributors: Müller, Rolf (Prof. Dr.) (Thesis advisor)
Format: Doctoral Thesis
Published: Philipps-Universität Marburg 2005
Online Access:PDF Full Text
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In the past years there were numerous finding in transcutaneus tumour vaccination. Langerhans cells have as dendritic cells of the epidermis a key role in the control of the immune system. Dendritic cells are important in tumour immunology, because they are antigen presenting cells and a key target for immunisation against tumour antigens. For malignant melanoma there are several strategies for transcutan vaccination against tumour antigens. Transcutaneous vaccination is difficult because of the robust protective shield of the skin. Hydrophile solutions can hardly pass the Stratum corneum to reach Langerhans cells. Up to now it was necessary to take away the Stratum corneum to induce a cytotoxic T-cell response. The results of transcutaneous application of Cyclosporin A with lipsome raise the question, if Liposome can have a use for application of tumour antigens. This method could work without taking away the Stratum corneum. In this thesis it is shown that Langerhans cells can get stimulated by the application of liposome of the intact skin. This is shown by a increase of CD86 expression. Langerhans cells enter a maturation process, that leads to a migration to the draining lymph nodes. The leukozyte population of the draining lymph nodes shows a increase of MHC II and CD 86 positiv cells. Liposomes can stimulate Langerhans cells effectively and are an interesting vehicle and adjuvants for transcutaneous vaccination.