Frontiers in Immunology (Jan 2021)

A T-Cell Surface Marker Panel Predicts Murine Acute Graft-Versus-Host Disease

  • Carina A. Bäuerlein,
  • Carina A. Bäuerlein,
  • Carina A. Bäuerlein,
  • Musga Qureischi,
  • Musga Qureischi,
  • Musga Qureischi,
  • Zeinab Mokhtari,
  • Zeinab Mokhtari,
  • Paula Tabares,
  • Paula Tabares,
  • Christian Brede,
  • Christian Brede,
  • Christian Brede,
  • Ana-Laura Jordán Garrote,
  • Ana-Laura Jordán Garrote,
  • Ana-Laura Jordán Garrote,
  • Simone S. Riedel,
  • Simone S. Riedel,
  • Simone S. Riedel,
  • Martin Chopra,
  • Martin Chopra,
  • Simone Reu,
  • Anja Mottok,
  • Estibaliz Arellano-Viera,
  • Estibaliz Arellano-Viera,
  • Carolin Graf,
  • Carolin Graf,
  • Miriam Kurzwart,
  • Miriam Kurzwart,
  • Katharina Schmiedgen,
  • Katharina Schmiedgen,
  • Hermann Einsele,
  • Hermann Einsele,
  • Matthias Wölfl,
  • Matthias Wölfl,
  • Paul-Gerhardt Schlegel,
  • Paul-Gerhardt Schlegel,
  • Andreas Beilhack,
  • Andreas Beilhack,
  • Andreas Beilhack

DOI
https://doi.org/10.3389/fimmu.2020.593321
Journal volume & issue
Vol. 11

Abstract

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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.

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