A T-Cell Surface Marker Panel Predicts Murine Acute Graft-Versus-Host Disease.
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.
['Bäuerlein|Carina A|CA|', 'Qureischi|Musga|M|', 'Mokhtari|Zeinab|Z|', 'Tabares|Paula|P|', 'Brede|Christian|C|', 'Jordán Garrote|Ana-Laura|AL|', 'Riedel|Simone S|SS|', 'Chopra|Martin|M|', 'Reu|Simone|S|', 'Mottok|Anja|A|', 'Arellano-Viera|Estibaliz|E|', 'Graf|Carolin|C|', 'Kurzwart|Miriam|M|', 'Schmiedgen|Katharina|K|', 'Einsele|Hermann|H|', 'Wölfl|Matthias|M|', 'Schlegel|Paul-Gerhardt|PG|', 'Beilhack|Andreas|A|']
D000208:Acute Disease D000818:Animals D015703:Antigens, CD D015415:Biomarkers D001706:Biopsy D004195:Disease Models, Animal D004198:Disease Susceptibility D005260:Female D006086:Graft vs Host Disease D018380:Hematopoietic Stem Cell Transplantation D051379:Mice D011379:Prognosis D016176:T-Lymphocyte Subsets D013601:T-Lymphocytes D014184:Transplantation, Homologous
prediction acute graft-versus-host disease transplantation mouse models alloreactive T cells