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Stem Cells

A high proportion of donor CD4+ T cells expressing the lymph node-homing chemokine receptor CCR7 increases incidence and severity of acute graft-versus-host disease in patients undergoing allogeneic stem cell transplantation for hematological malignancy

Leukemia volume 20, pages 1557–1565 (2006)Cite this article

Abstract

CC-chemokine receptor 7 (CCR7), a chemokine receptor required for transmigration into lymphoid organs, is only expressed by naive and central memory T cells. T cells with a capacity of homing into lymphoid organs can initiate acute graft-versus-host disease (GVHD) in mice and respond vigorously in vitro to alloantigens in humans, but their impact on clinical outcomes is unknown. We evaluated prospectively the distribution of naive, central memory and CCR7neg memory T-cell subsets in 39 bone marrow and 23 granulocyte colony-stimulating factor-mobilized peripheral blood stem cell allografts and investigated their impact on patient outcomes. Ranges of the relative proportions of CCR7+ cells within CD4+ and CD8+ T-cell populations were broad, but did not differ between the two sources of allografts. By multivariate analysis, high percentage of donor-derived CD4+CCR7+ T cells (>73.5%) significantly correlated with incidence, earliness of onset and severity of acute GVHD, conferring the highest adjusted hazard ratio (HR=3.9; 95% confidence interval 1.4–10.8; P=0.008) without interfering in other clinical events, especially chronic GVHD and relapse. Determination of the percentage of CD4+CCR7+ T cells in the graft provides a predictive indicator of acute GVHD. Partial depletion of this subset may reduce the risk of acute GVHD while preserving immunotherapeutic effects.

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Acknowledgements

We thank Dr Léonardo Magro, Dr Stéphane Darré, the hematology fellows and other senior physicians. We are especially grateful to Sandrine Apaza-Lopez, Jacques Trauet, Véronique Lekeux, Virginie Dutriez and staffs involved in the care of the BMT unit. We also thank all the donors and patients who agreed to be enrolled in this study.

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  1. I Yakoub-Agha and P Saule: These authors contributed equally to this work

Authors and Affiliations

  1. Service des Maladies du Sang, UAM allogreffes de CSH, Hopital Huriez, CHRU de Lille, Lille Cedex, France

    I Yakoub-Agha, S Depil, J-B Micol, F Bauters & J-P Jouet

  2. Laboratoire d’Immunologie, EA2686, IFR114, CHU – Université de Lille 2, Lille, France

    P Saule, C Grutzmacher, J-P Dessaint & M Labalette

  3. Etablissement Français du Sang, Thérapie cellulaire, Lille, France

    S Depil & F Boulanger-Villard

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Yakoub-Agha, I., Saule, P., Depil, S. et al. A high proportion of donor CD4+ T cells expressing the lymph node-homing chemokine receptor CCR7 increases incidence and severity of acute graft-versus-host disease in patients undergoing allogeneic stem cell transplantation for hematological malignancy. Leukemia 20, 1557–1565 (2006). https://doi.org/10.1038/sj.leu.2404308

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