TY  - JOUR
A1  - Jarick, Katja J.
A1  - Mokhtari, Zeinab
A1  - Scheller, Lukas
A1  - Hartweg, Julia
A1  - Thusek, Sina
A1  - Le, Duc-Dung
A1  - Ranecky, Maria
A1  - Shaikh, Haroon
A1  - Qureischi, Musga
A1  - Heinze, Katrin G.
A1  - Beilhack, Andreas
T1  - Photoconversion of Alloreactive T Cells in Murine Peyer’s Patches During Acute Graft-Versus-Host Disease: Tracking the Homing Route of Highly Proliferative Cells In Vivo
JF  - Frontiers in Immunology
N2  - The regulation of immune cell migration throughout the body is essential to warrant immunosurveillance and to maintain immune homeostasis. Marking and tracking of these cells has proven important to study mechanisms of immune cell trafficking and cell interaction in vivo. Photoconversion is a well-suited technique for intravital application because it enables contactless time- and location-specific marking of cells in the tissue without surgically manipulating the microenvironment of the cells in question. However, in dividing cells the converted fluorescent protein may decline quickly. Here, we provide a detailed description of the photoconversion technique and its applicability to tracking highly proliferating T cells from the priming site of T cell activation to peripheral target organs of effector function in a preclinical model. Dendra2+ T cells were photoconverted in the Peyer’s patches during the initiation phase of acute graft-versus-host disease (GvHD) and tracked through the mesenteric lymph nodes and the peripheral blood to the small intestine with flow cytometry and intravital two-photon microscopy. Photoconverted alloreactive T cells preserved the full proliferative capacity, homing, and migration of alloreactive T cells in the intestinal lamina propria. We conclusively proved that photoconversion of highly proliferative alloreactive T cells in the Peyer’s patches is an effective tool to study trafficking of alloreactive T cells under physiologic conditions and to GvHD target tissues. This technique can also be applied to the study of immune cell tracking under inflammatory and non-inflammatory conditions.
KW  - T cell migration
KW  - acute graft-versus-host disease
KW  - mouse models
KW  - photoconversion
KW  - Dendra2
KW  - Peyer's patch
KW  - in vivo cell tracking
KW  - lymphocyte homing
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-323309
VL  - 9
ER  - 
TY  - JOUR
A1  - Bäuerlein, Carina A.
A1  - Qureischi, Musga
A1  - Mokhtari, Zeinab
A1  - Tabares, Paula
A1  - Brede, Christian
A1  - Jordán Garrote, Ana-Laura
A1  - Riedel, Simone S.
A1  - Chopra, Martin
A1  - Reu, Simone
A1  - Mottok, Anja
A1  - Arellano-Viera, Estibaliz
A1  - Graf, Carolin
A1  - Kurzwart, Miriam
A1  - Schmiedgen, Katharina
A1  - Einsele, Hermann
A1  - Wölfl, Matthias
A1  - Schlegel, Paul-Gerhardt
A1  - Beilhack, Andreas
T1  - A T-Cell Surface Marker Panel Predicts Murine Acute Graft-Versus-Host Disease
JF  - Frontiers in Immunology
N2  - Acute graft-versus-host disease (aGvHD) is a severe and often life-threatening complication of allogeneic hematopoietic cell transplantation (allo-HCT). AGvHD is mediated by alloreactive donor T-cells targeting predominantly the gastrointestinal tract, liver, and skin. Recent work in mice and patients undergoing allo-HCT showed that alloreactive T-cells can be identified by the expression of α4β7 integrin on T-cells even before manifestation of an aGvHD. Here, we investigated whether the detection of a combination of the expression of T-cell surface markers on peripheral blood (PB) CD8\(^+\) T-cells would improve the ability to predict aGvHD. To this end, we employed two independent preclinical models of minor histocompatibility antigen mismatched allo-HCT following myeloablative conditioning. Expression profiles of integrins, selectins, chemokine receptors, and activation markers of PB donor T-cells were measured with multiparameter flow cytometry at multiple time points before the onset of clinical aGvHD symptoms. In both allo-HCT models, we demonstrated a significant upregulation of α4β7 integrin, CD162E, CD162P, and conversely, a downregulation of CD62L on donor T-cells, which could be correlated with the development of aGvHD. Other surface markers, such as CD25, CD69, and CC-chemokine receptors were not found to be predictive markers. Based on these preclinical data from mouse models, we propose a surface marker panel on peripheral blood T-cells after allo-HCT combining α4β7 integrin with CD62L, CD162E, and CD162P (cutaneous lymphocyte antigens, CLA, in humans) to identify patients at risk for developing aGvHD early after allo-HCT.
KW  - acute graft-versus-host disease
KW  - alloreactive T cells
KW  - transplantation
KW  - prediction
KW  - mouse models
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224290
SN  - 1664-3224
VL  - 11
ER  - 
TY  - JOUR
A1  - Klein-Hessling, Stefan
A1  - Muhammad, Khalid
A1  - Klein, Matthias
A1  - Pusch, Tobias
A1  - Rudolf, Ronald
A1  - Flöter, Jessica
A1  - Qureischi, Musga
A1  - Beilhack, Andreas
A1  - Vaeth, Martin
A1  - Kummerow, Carsten
A1  - Backes, Christian
A1  - Schoppmeyer, Rouven
A1  - Hahn, Ulrike
A1  - Hoth, Markus
A1  - Bopp, Tobias
A1  - Berberich-Siebelt, Friederike
A1  - Patra, Amiya
A1  - Avots, Andris
A1  - Müller, Nora
A1  - Schulze, Almut
A1  - Serfling, Edgar
T1  - NFATc1 controls the cytotoxicity of CD8\(^{+}\) T cells
JF  - Nature Communications
N2  - Cytotoxic T lymphocytes are effector CD8\(^{+}\) T cells that eradicate infected and malignant cells. Here we show that the transcription factor NFATc1 controls the cytotoxicity of mouse cytotoxic T lymphocytes. Activation of Nfatc1\(^{-/-}\) cytotoxic T lymphocytes showed a defective cytoskeleton organization and recruitment of cytosolic organelles to immunological synapses. These cells have reduced cytotoxicity against tumor cells, and mice with NFATc1-deficient T cells are defective in controlling Listeria infection. Transcriptome analysis shows diminished RNA levels of numerous genes in Nfatc1\(^{-/-}\) CD8\(^{+}\) T cells, including Tbx21, Gzmb and genes encoding cytokines and chemokines, and genes controlling glycolysis. Nfatc1\(^{-/-}\), but not Nfatc2\(^{-/-}\) CD8\(^{+}\) T cells have an impaired metabolic switch to glycolysis, which can be restored by IL-2. Genome-wide ChIP-seq shows that NFATc1 binds many genes that control cytotoxic T lymphocyte activity. Together these data indicate that NFATc1 is an important regulator of cytotoxic T lymphocyte effector functions.
KW  - cytotoxic T cells
KW  - lymphocyte activation
KW  - signal transduction
KW  - gene regulation
KW  - immune cells
KW  - NFATc1
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170353
VL  - 8
IS  - 511
ER  -