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Abstract
Observations from Majewski et al. showed that Rottlerin has an effect on the classical antigen
presentation by BMDC to OT-II cells. Based on these insights, I found out that Rottlerin had also an
effect on the cross-presentation by BMDC to OT-I cells. Summing, my in vitro results together with
the results of Majewski et al. pointed out at which locations Rottlerin acts during the MHC-I- and
MHC-II-associated peptide presentation. Moreover I could answer the questions, which Majewski et
al. left open. On the one hand I could reveal that Rottlerin inhibited the upregulation of
costimulatory molecules, on the other hand that it has a direct effect on the activation of T cells. In
this thesis I could also establish possible in vivo experiments for the future use of Rottlerin and to
prove in future experiments whether Rottlerin also inhibits indirectly or directly the activation of
CD8+ T cells. According to my findings for CD8+ OT-I cells and the in vitro results of Majewski et al.
for the restricted activation of CD4+ T cells it was suggested to review the functionality of diverse in
vivo disease models which are dependent on T cells. In the established models of POI, AdGOLinduced
liver injury, the NTN and T1D Rottlerin could cause the reduction of the disease parameters
in the development of the investigated disorders. The adjustment of the administration time, -
species and –frequency could also show effects on other disease models. Recently, with the aid of
floxed mice it could be validated whether the described in vivo effects of Rottlerin are only or partly
PKCδ-dependent. In future, on the one hand, the basic mechanism from Rottlerin on immune
processes, and on the other hand, the effect of Rottlerin on further disease models could be
investigated. The Investigations are admittedly not complete, however the potential
immunomodulatory effect of Rottlerin could be enhanced to use it as future therapeutic agent.
Review
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Supervisor:
Dates
Created: 2019Issued: 2019-11-05Updated: 2019-11-05
Faculty
Medizin
Publisher
Philipps-Universität Marburg
Language
ger
Data types
DoctoralThesis
Keywords
T-ZellaktivierungAutoimmunkrankheitenKreuzpräsentationImmunologie
DFG-subjects
PKCKreuzpräsentationT-ZellaktivierungRottlerin
DDC-Numbers
610
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Heineck, Lukas: Der Einfluss von Rottlerin auf T-Zellpräsentation und -aktivierung. : Philipps-Universität Marburg 2019-11-05. DOI: https://doi.org/10.17192/z2019.0426.