A high migratory capacity of donor T-cells in response to the lymph node homing receptor CCR7 increases the incidence and severity of GvHD
| Autor: | Beatriz Colom-Fernández, V López-Huete, Cecilia Muñoz-Calleja, Ana Marcos-Jiménez, Itxaso Portero-Sainz, Carlos Cuesta-Mateos, C Fernández-Arandojo, Beatriz Somovilla-Crespo, Anna Kreutzman, A de Rosendo-Serrano, V Gómez-García de Soria, Mercedes Royg, A Ramírez-Mengíbar, Lorena Vega-Piris |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Adult
CD4-Positive T-Lymphocytes Male Receptors CCR7 Adolescent CD4-CD8 Ratio Receptors Lymphocyte Homing Graft vs Host Disease chemical and pharmacologic phenomena C-C chemokine receptor type 7 Severity of Illness Index Pathogenesis 03 medical and health sciences Young Adult 0302 clinical medicine immune system diseases medicine Humans Transplantation Homologous Prospective Studies L-Selectin Lymphocyte homing receptor Aged Transplantation Chemokine CCL21 business.industry Chemotaxis Incidence CCL19 virus diseases hemic and immune systems Hematology Middle Aged medicine.disease Tissue Donors surgical procedures operative Graft-versus-host disease 030220 oncology & carcinogenesis Immunology Chemokine CCL19 Female business CD8 030215 immunology Homing (hematopoietic) |
| Zdroj: | Bone marrow transplantation. 52(5) |
| ISSN: | 1476-5365 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink