A T-Cell Surface Marker Panel Predicts Murine Acute Graft-Versus-Host Disease
Baeuerlein CA, Qureischi M, Mokhtari Z, Tabares P, Brede C, Garrote ALJ, Riedel SS, Chopra M, Reu S, Mottok A, Arellano-Viera E, Graf C, Kurzwart M, Schmiedgen K, Einsele H, Woelfl M, Schlegel PG, Beilhack A (2021)
Publication Type: Journal article
Publication year: 2021
Journal
Book Volume: 11
Article Number: 593321
DOI: 10.3389/fimmu.2020.593321
Abstract
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.
Involved external institutions
Germany (DE)How to cite
APA:
Baeuerlein, C.A., Qureischi, M., Mokhtari, Z., Tabares, P., Brede, C., Garrote, A.-L.J.,... Beilhack, A. (2021). A T-Cell Surface Marker Panel Predicts Murine Acute Graft-Versus-Host Disease. Frontiers in Immunology, 11. https://dx.doi.org/10.3389/fimmu.2020.593321
MLA:
Baeuerlein, Carina A., et al. "A T-Cell Surface Marker Panel Predicts Murine Acute Graft-Versus-Host Disease." Frontiers in Immunology 11 (2021).
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