Gas6 deficiency in recipient mice of allogeneic transplantation alleviates hepatic graft-versus-host disease
| Autor: | Anne C. Brisset, Rocco Sugamele, François Saller, Anne Angelillo-Scherrer, Françoise Bono, Linda Kadi, Shozo Izui, J M Herbert, Laurent Burnier, Peter Carmeliet, Marc Schapira, Lucie Clementine Baudino |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Allogeneic transplantation
T-Lymphocytes medicine.medical_treatment Lymphocyte Immunology Graft vs Host Disease Hematopoietic stem cell transplantation Cell Separation Biology ddc:616.07 Endothelial Cells/metabolism Lymphocyte Activation/immunology Lymphocyte Activation Biochemistry Flow cytometry Mice Liver/*immunology/pathology medicine Animals Transplantation Homologous Graft vs Host Disease/genetics/immunology/*prevention & control Mice Knockout Transplantation medicine.diagnostic_test Reverse Transcriptase Polymerase Chain Reaction T-Lymphocytes/cytology/immunology/metabolism Hematopoietic Stem Cell Transplantation Endothelial Cells Cell Biology Hematology Chemotaxis Leukocyte/genetics/immunology medicine.disease Flow Cytometry Immunohistochemistry Chemotaxis Leukocyte medicine.anatomical_structure Graft-versus-host disease Liver Hematopoietic Stem Cell Transplantation/*adverse effects Intercellular Signaling Peptides and Proteins Tumor necrosis factor alpha Bone marrow Lymphocyte Culture Test Mixed Intercellular Signaling Peptides and Proteins/*deficiency/genetics |
| Zdroj: | Blood, Vol. 115, No 16 (2010) pp. 3390-3397 |
| ISSN: | 0006-4971 |
| Popis: | Growth arrest-specific gene 6 (Gas6) is expressed in antigen-presenting cells and endothelial cells (ECs) but not in T cells. When wild-type (WT) or Gas6−/− mice received allogeneic non–T cell–depleted bone marrow cells, hepatic graft-versus-host disease (GVHD) was alleviated in Gas6−/− recipients regardless of donor genotype, but not in WT recipients. T-cell infiltration was more prominent and diffuse in WT than in Gas6−/− recipients' liver. When mice received 0.5 × 106 allogeneic T cells with T cell–depleted allogeneic bone marrow, clinical signs indicated that GVHD was less severe in Gas6−/− than in WT recipients, as shown by a significant improvement of the survival and reduced liver GVHD. These data demonstrate that donor cells were not involved in the protection mechanism. In addition, lack of Gas6 in antigen-presenting cells did not affect WT or Gas6−/− T-cell proliferation. We therefore assessed the response of WT or Gas6−/− ECs to tumor necrosis factor-α. Lymphocyte transmigration was less extensive through Gas6−/− than WT ECs and was not accompanied by increases in adhesion molecule levels. Thus, the lack of Gas6 in ECs impaired donor T-cell transmigration into the liver, providing a rationale for considering Gas6 pathway as a potential nonimmunosuppressive target to minimize GVHD in patients receiving allogeneic hematopoietic stem cell transplantation. |
| Databáze: | OpenAIRE |
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