Publikationsserver der RWTH Aachen University
Untersuchungen HLA-Klasse II-assoziierter, T-zellvermittelter Autoimmunität im humanisierten SCID-Mausmodell des Pemphigus vulgaris
Abstract
dc:descriptionPemphigus vulgaris (PV) is a severe bullous autoimmune skin disease which is caused by autoantibodies against an epidermal adhesion protein, desmoglein 3 (DG3). The underlying cellular mechanisms in the pathogenesis of PV are not yet completely understood. PV is associated with particular HLA class II alleles. The aim of this study was to examine the function of autoreactive T-lymphocytes in the regulation of autoantibody production and the importance of immunogenetic factors in T-cell activation in an in vivo model. The humanized SCID mouse model allows the adoptive transfer of human peripheral blood lymphocytes (PBL) to establish a functional human immune system within the murine organism. PBL from a patient with active PV disease, from a HLA-homologous healthy control and from a healthy control without an PV-associated HLA-genotype were used. The human PBL were either incubated with the autoantigen DG3 prior to injection or were boosted several times with DG3 after cell transfer. After 8 weeks, human immunoglobulin could be detected in substantial amounts in all mice sera which is a proof for the successful induction of a humanized in vivo model. In the blood sample as well as in skin and tongue of one mouse which was reconstituted with PBL from the PV patient which were boosted with DG3 following the transfer, human antidesmosomal antibodies of the IgM isotype could be detected. Human autoantibodies against DG3 could not be shown in blood and tissue of the other SCID mice. The induction of a functional human immune system was successful in all mice. Nonetheless the efficacy of this model to induce human autoantibodies against DG3 is too small. Possible reasons could be the relatively low frequency of autoreactive T-cells in the peripheral blood of PV patients, an anergic state of human PBL due to the excessive contact to murine xenoantigens and a possibly toxic effect of DG3 in high concentrations during the in vitro incubation or the in vivo immunization.
Degree
thesis:*- Grantor dc:publisher
- Publikationsserver der RWTH Aachen University
- Year dc:date
- 2003
Author and committee
dc:creator, dc:contributor.*- Author dc:creator
-
- Rädisch, Thomas
- Contributors dc:contributor
-
- Hertl, Michael
Subjects
dc:subject × 6Rights
dc:rights- Statement dc:rights
-
- info:eu-repo/semantics/openAccess
- Language dc:language
- ger
Identifiers
dc:identifier.*- OAI identifier oai:identifier
- oai:publications.rwth-aachen.de:62200