TY  - JOUR
A1  - Haack, Stephanie
A1  - Baiker, Sarah
A1  - Schlegel, Jan
A1  - Sauer, Markus
A1  - Sparwasser, Tim
A1  - Langenhorst, Daniela
A1  - Beyersdorf, Niklas
T1  - Superagonistic CD28 stimulation induces IFN‐γ release from mouse T helper 1 cells in vitro and in vivo
JF  - European Journal of Immunology
N2  - Like human Th1 cells, mouse Th1 cells also secrete IFN‐γ upon stimulation with a superagonistic anti‐CD28 monoclonal antibody (CD28‐SA). Crosslinking of the CD28‐SA via FcR and CD40‐CD40L interactions greatly increased IFN‐γ release. Our data stress the utility of the mouse as a model organism for immune responses in humans.
KW  - CD28
KW  - Th1 cells
KW  - cytokine release
KW  - interferon γ
KW  - Superagonistic antibody
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-239028
VL  - 51
IS  - 3
SP  - 738
EP  - 741
ER  - 
TY  - JOUR
A1  - Zadeh-Khorasani, Maryam
A1  - Nolte, Thomas
A1  - Mueller, Thomas D.
A1  - Pechlivanis, Markos
A1  - Rueff, Franziska
A1  - Wollenberg, Andreas
A1  - Fricker, Gert
A1  - Wolf, Eckhard
A1  - Siebeck, Matthias
A1  - Gropp, Roswitha
T1  - NOD-scid IL2R \(\gamma^{null}\) mice engrafted with human peripheral blood mononuclear cells as a model to test therapeutics targeting human signaling pathways
JF  - Journal of Translational Medicine
N2  - Background: Animal models of human inflammatory diseases have limited predictive quality for human clinical trials for various reasons including species specific activation mechanisms and the immunological background of the animals which markedly differs from the genetically heterogeneous and often aged patient population. 
Objective: Development of an animal model allowing for testing therapeutics targeting pathways involved in the development of Atopic Dermatitis (AD) with better translatability to the patient. 
Methods: NOD-scid IL2R \(\gamma^{null}\) mice engrafted with human peripheral blood mononuclear cells (hPBMC) derived from patients suffering from AD and healthy volunteers were treated with IL-4 and the antagonistic IL-4 variant R121/Y124D (Pitrakinra). Levels of human (h) IgE, amount of B-, T- and plasma-cells and ratio of CD4 : CD8 positive cells served as read out for induction and inhibition of cell proliferation and hIgE secretion. Results were compared to in vitro analysis. 
Results: hIgE secretion was induced by IL-4 and inhibited by the IL-4 antagonist Pitrakinra in vivo when formulated with methylcellulose. B-cells proliferated in response to IL-4 in vivo; the effect was abrogated by Pitrakinra. IL-4 shifted CD4 : CD8 ratios in vitro and in vivo when hPBMC derived from healthy volunteers were used. Pitrakinra reversed the effect. Human PBMC derived from patients with AD remained inert and engrafted mice reflected the individual responses observed in vitro. 
Conclusion: NOD-scid IL2R \(\gamma^{null}\) mice engrafted with human PBMC reflect the immunological history of the donors and provide a complementary tool to in vitro studies. Thus, studies in this model might provide data with better translatability from bench to bedside.
KW  - atopic dermatitis
KW  - T-cells
KW  - rheumatoid arthritis
KW  - human interleukin-4
KW  - TGN1412
KW  - oxazolone colitis
KW  - cytokine release
KW  - expression
KW  - antagonists
KW  - responses
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-122960
SN  - 1479-5876
VL  - 11
IS  - 4
ER  -