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Graft-Versus-Host Disease

A high migratory capacity of donor T-cells in response to the lymph node homing receptor CCR7 increases the incidence and severity of GvHD

Bone Marrow Transplantation volume 52, pages 745–752 (2017)Cite this article

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Abstract

The pathogenesis of GvHD involves migration of donor T-cells into the secondary lymphoid organs in the recipient, which is steered by two homing molecules, CD62L and CCR7. Therefore, we investigated whether the migratory capacity of donor T-cells is associated with GvHD. This single center prospective study included 85 donor–recipient pairs. In vitro chemotaxis assays of the lymphocytes of the apheresis product were performed in parallel to the analysis of CD62L and CCR7 by flow cytometry. The migratory index to the CCR7 ligands, CCL19 and CCL21, was higher in T-cells from donors whose recipients will develop GvHD. Similarly, the acute GvHD (aGvHD) group received higher percentage of CD4+CCR7+ T-cells, whereas chronic GvHD (cGvHD) patients were transplanted with higher percentages of CD8+CCR7+ T-cells compared with the non-GvHD group. These results were confirmed when patients were subdivided according to degrees of severity. Further, multivariate analysis confirmed that the proportions of CCR7+ CD4+ and CCR7+ CD8+ T-cells are risk factors for the development and severity of aGvHD and cGvHD, respectively. Functional experiments demonstrated that CCR7+ T-cells exhibited higher potential for activation than CCR7- T-cells did. We therefore propose that the selective depletion of CCR7-expressing T-cells may be an effective preventive therapy for GvHD.

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Acknowledgements

Grant PI12/00494 from the Fondo de Investigaciones Sanitarias to CMC supported this work. CMC was co-financed by FEDER funds. We are grateful to Miguel Vicente-Manzanares, PhD, for critical comments on experimental procedures.

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Authors and Affiliations

  1. Department of Immunology, Instituto de Investigación Sanitaria Princesa, Hospital Universitario de La Princesa, Madrid, Spain

    I Portero-Sainz, B Colom-Fernández, A Marcos-Jiménez, B Somovilla-Crespo, A Ramírez-Mengíbar, V López-Huete, A de Rosendo-Serrano, A Kreutzman & C Muñoz-Calleja

  2. Department of Hematology, Instituto de Investigación Sanitaria Princesa, Hospital Universitario de La Princesa, Madrid, Spain

    V Gómez-García de Soria, C Fernández-Arandojo & M Royg

  3. IMMED S.L., Immunological and Medicinal Products, Madrid, Spain

    C Cuesta-Mateos

  4. Department of Statistics, Instituto de Investigación Sanitaria Princesa, Hospital Universitario de La Princesa, Madrid, Spain

    L Vega-Piris

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  1. I Portero-Sainz
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Correspondence to C Muñoz-Calleja.

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C Cuesta-Mateos is in an employment relationship with the company IMMED. The remaining authors declare no conflict of interest.

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Portero-Sainz, I., Gómez-García de Soria, V., Cuesta-Mateos, C. et al. A high migratory capacity of donor T-cells in response to the lymph node homing receptor CCR7 increases the incidence and severity of GvHD. Bone Marrow Transplant 52, 745–752 (2017). https://doi.org/10.1038/bmt.2016.342

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