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
| Autor: | Francis Bauters, Boulanger-Villard F, C. Grutzmacher, Ibrahim Yakoub-Agha, Jean-Baptiste Micol, Myriam Labalette, Pasquine Saule, Jean Paul Dessaint, Stéphane Depil, J P Jouet |
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| Rok vydání: | 2006 |
| Předmět: |
Adult
CD4-Positive T-Lymphocytes Receptors CCR7 Cancer Research Adolescent Graft vs Host Disease chemical and pharmacologic phenomena C-C chemokine receptor type 7 Biology Severity of Illness Index Recurrence medicine Humans Transplantation Homologous Child Lymph node Aged Incidence Hematology Middle Aged Flow Cytometry Survival Analysis Transplantation surgical procedures operative Lymphatic system medicine.anatomical_structure Oncology Child Preschool Hematologic Neoplasms Immunology Receptors Chemokine Bone marrow Stem cell CD8 Stem Cell Transplantation Homing (hematopoietic) |
| Zdroj: | Leukemia. 20:1557-1565 |
| ISSN: | 1476-5551 0887-6924 |
| DOI: | 10.1038/sj.leu.2404308 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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