title: A high migratory capacity of donor T-cells in response to the lymph node homing receptor CCR7 increases the incidence and severity of GvHD.
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.
authors.affiliation: Department of Immunology, Instituto de Investigación Sanitaria Princesa, Hospital Universitario de La Princesa, Madrid, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Portero-Sainz
authors.affiliation: Department of Hematology, Instituto de Investigación Sanitaria Princesa, Hospital Universitario de La Princesa, Madrid, Spain.
authors.forename: V
authors.initials: V
authors.lastname: Gómez-García de Soria
authors.affiliation: IMMED S.L., Immunological and Medicinal Products, Madrid, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Cuesta-Mateos
authors.affiliation: Department of Hematology, Instituto de Investigación Sanitaria Princesa, Hospital Universitario de La Princesa, Madrid, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Fernández-Arandojo
authors.affiliation: Department of Statistics, Instituto de Investigación Sanitaria Princesa, Hospital Universitario de La Princesa, Madrid, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Vega-Piris
authors.affiliation: Department of Hematology, Instituto de Investigación Sanitaria Princesa, Hospital Universitario de La Princesa, Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Royg
authors.affiliation: Department of Immunology, Instituto de Investigación Sanitaria Princesa, Hospital Universitario de La Princesa, Madrid, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Colom-Fernández
authors.affiliation: Department of Immunology, Instituto de Investigación Sanitaria Princesa, Hospital Universitario de La Princesa, Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Marcos-Jiménez
authors.affiliation: Department of Immunology, Instituto de Investigación Sanitaria Princesa, Hospital Universitario de La Princesa, Madrid, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Somovilla-Crespo
authors.affiliation: Department of Immunology, Instituto de Investigación Sanitaria Princesa, Hospital Universitario de La Princesa, Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Ramírez-Mengíbar
authors.affiliation: Department of Immunology, Instituto de Investigación Sanitaria Princesa, Hospital Universitario de La Princesa, Madrid, Spain.
authors.forename: V
authors.initials: V
authors.lastname: López-Huete
authors.affiliation: Department of Immunology, Instituto de Investigación Sanitaria Princesa, Hospital Universitario de La Princesa, Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: de Rosendo-Serrano
authors.affiliation: Department of Immunology, Instituto de Investigación Sanitaria Princesa, Hospital Universitario de La Princesa, Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Kreutzman
authors.affiliation: Department of Immunology, Instituto de Investigación Sanitaria Princesa, Hospital Universitario de La Princesa, Madrid, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Muñoz-Calleja
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000637:transplantation; D054415:Chemokine CCL19 / Q000032:analysis; D054421:Chemokine CCL21 / Q000032:analysis; D002633:Chemotaxis; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000473:pathology*; D006801:Humans; D015994:Incidence; D019041:L-Selectin / Q000032:analysis; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D054400:Receptors, CCR7 / Q000032:analysis* / Q000276:immunology; D016201:Receptors, Lymphocyte Homing / Q000502:physiology; D012720:Severity of Illness Index; D014019:Tissue Donors; D014184:Transplantation, Homologous / Q000009:adverse effects; D055815:Young Adult
chemical_list: C515460:CCL19 protein, human; C515478:CCL21 protein, human; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D054400:Receptors, CCR7; D016201:Receptors, Lymphocyte Homing; D019041:L-Selectin