Burnier, Laurent Saller, François Kadi, Linda Brisset, Anne C Sugamele, Rocco Baudino, Lucie Bono, Françoise Herbert, Jean-Marc Carmeliet, Peter Schapira, Marc Izui, Shozo Angelillo-Scherrer, Anne # ×
Blood vol:115 issue:16 pages:3390-3397
Growth arrest-specific gene 6 (Gas6) is expressed in antigen-presenting cells (APCs) and endothelial cells (ECs) but not in T-cells. When WT or Gas6(-/-) mice received allogeneic non-T-cell-depleted bone marrow cells, hepatic graft-versus-host disease (GVHD) was alleviated in Gas6(-/-) recipients whatever was the 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 x 10(6) 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 demonstrated that donor cells were not involved in the protection mechanism. In addition, lack of Gas6 in APCs did not affect WT or Gas6(-/-) T-cell proliferation. We therefore assessed the response of WT or Gas6(-/-) ECs to TNF-alpha. Lymphocyte transmigration was less extensive through Gas6(-/-) than WT ECs and was not accompanied by increases in adhesion molecules levels. Thus, lack of Gas6 in ECs impaired donor T-cells transmigration into the liver providing a rationale for considering Gas6 pathway as a potential non-immunosuppressive target to minimize GVHD in patients receiving allogeneic hematopoietic stem cell transplantation.