TY  - JOUR
A1  - Shaikh, Haroon
A1  - Vargas, Juan Gamboa
A1  - Mokhtari, Zeinab
A1  - Jarick, Katja J.
A1  - Ulbrich, Maria
A1  - Mosca, Josefina Peña
A1  - Viera, Estibaliz Arellano
A1  - Graf, Caroline
A1  - Le, Duc-Dung
A1  - Heinze, Katrin G.
A1  - Büttner-Herold, Maike
A1  - Rosenwald, Andreas
A1  - Pezoldt, Joern
A1  - Huehn, Jochen
A1  - Beilhack, Andreas
T1  - Mesenteric Lymph Node Transplantation in Mice to Study Immune Responses of the Gastrointestinal Tract
JF  - Frontiers in Immunology
N2  - Mesenteric lymph nodes (mLNs) are sentinel sites of enteral immunosurveillance and immune homeostasis. Immune cells from the gastrointestinal tract (GIT) are constantly recruited to the mLNs in steady-state and under inflammatory conditions resulting in the induction of tolerance and immune cells activation, respectively. Surgical dissection and transplantation of lymph nodes (LN) is a technique that has supported seminal work to study LN function and is useful to investigate resident stromal and endothelial cell biology and their cellular interactions in experimental disease models. Here, we provide a detailed protocol of syngeneic mLN transplantation and report assays to analyze effective mLN engraftment in congenic recipients. Transplanted mLNs allow to study T cell activation and proliferation in preclinical mouse models. Donor mLNs proved viable and functional after surgical transplantation and regenerated blood and lymphatic vessels. Immune cells from the host completely colonized the transplanted mLNs within 7-8 weeks after the surgical intervention. After allogeneic hematopoietic cell transplantation (allo-HCT), adoptively transferred allogeneic CD4+ T cells from FVB/N (H-2q) mice homed to the transplanted mLNs in C57BL/6 (H-2b) recipients during the initiation phase of acute graft-versus-host disease (aGvHD). These CD4+ T cells retained full proliferative capacity and upregulated effector and gut homing molecules comparable to those in mLNs from unmanipulated wild-type recipients. Wild type mLNs transplanted into MHCII deficient syngeneic hosts sufficed to activate alloreactive T cells upon allogeneic hematopoietic cell transplantation, even in the absence of MHCII+ CD11c+ myeloid cells. These data support that orthotopically transplanted mLNs maintain physiological functions after transplantation. The technique of LN transplantation can be applied to study migratory and resident cell compartment interactions in mLNs as well as immune reactions from and to the gut under inflammatory and non-inflammatory conditions.
KW  - acute graft-versus host disease
KW  - alloreactive T cells
KW  - mesenteric lymph node
KW  - lymph node transplantation
KW  - mouse models
KW  - lymph node stromal cells
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-244869
SN  - 1664-3224
VL  - 12
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  -