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CD4+Foxp3+ regulatory T cells prolong drug-induced disease remission in (NZBxNZW) F1 lupus mice
Weigert, Olivia

HaupttitelCD4+Foxp3+ regulatory T cells prolong drug-induced disease remission in (NZBxNZW) F1 lupus mice
TitelvarianteVerlängerung einer medikamentös induzierten Krankheitsremission durch regulatorische T-Zellen im (NZBxNZW) F1 Lupus-Mausmodell des SLE
AutorWeigert, Olivia
Geburtsort: Bad Belzig
GutachterN.N.
weitere GutachterN.N.
Freie Schlagwörterregulatory T cells; systemic lupus erythematosus; immunotherapy; CD4+Foxp3+ Treg
DDC610 Medizin und Gesundheit
ZusammenfassungIntroduction: The ability to ameliorate murine lupus renders regulatory T cells (Treg) a promising tool for the treatment of systemic lupus erythematosus (SLE). In consideration to the clinical translation of a Treg-based immunotherapy of SLE, we explored the potential of CD4+Foxp3+ Treg to maintain disease remission after induction of remission with an established cyclophosphamide (CTX) regimen in lupus-prone (NZBxNZW) F1 mice. As a prerequisite for this combined therapy, we also investigated the impact of CTX on the biology of endogenous Treg and conventional CD4+ T cells (Tcon).
Methods: Remission of disease was induced in diseased (NZBxNZW) F1 mice with an established CTX regimen consisting of a single dose of glucocorticosteroids followed by five day course with daily injections of CTX. Five days after the last CTX injection, differing amounts of purified CD4+Foxp3+CD25+ Treg were adoptively transferred and clinical parameters, autoantibody titers, the survival and changes in peripheral blood lymphocyte subsets were determined at different time points during the study. The influence of CTX on the numbers, frequencies and proliferation of endogenous Treg and Tcon was analyzed in lymphoid organs by flow cytometry.
Results: Apart from abrogating the proliferation of Tcon, we found that treatment with CTX induced also a significant inhibition of Treg proliferation and a decline in Treg numbers in lymphoid organs. Additional adoptive transfer of 1.5 × 106 purified Treg after the CTX regimen significantly increased the survival and prolonged the interval of remission by approximately five weeks compared to mice that received only the CTX regimen. The additional clinical amelioration was associated with an increase in the Treg frequency in the peripheral blood indicating a compensation of CTX-induced Treg deficiency by the Treg transfer.
Conclusions: Treg were capable to prolong the interval of remission induced by conventional cytostatic drugs. This study provides valuable information and a first proof-of-concept for the feasibility of a Treg-based immunotherapy in the maintenance of disease remission in SLE.
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Fachbereich/EinrichtungMedizinische Fakultät Charité - Universitätsmedizin Berlin
Erscheinungsjahr2014
Dokumententyp/-SammlungenDissertation
Medientyp/FormatText
SpracheEnglisch
Rechte Nutzungsbedingungen
Tag der Disputation05.12.2014
Erstellt am26.11.2014 - 14:08:36
Letzte Änderung26.11.2014 - 14:11:58
 
Statische URLhttp://edocs.fu-berlin.de/diss/receive/FUDISS_thesis_000000097682
URNurn:nbn:de:kobv:188-fudissthesis000000097682-4
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