CD4+ invariant natural killer T cells protect from murine GVHD lethality through expansion of donor CD4+CD25+FoxP3+ regulatory T cells.

Autor:	Schneidawind D; Division of Blood and Marrow Transplantation, Department of Medicine., Pierini A; Division of Blood and Marrow Transplantation, Department of Medicine., Alvarez M; Division of Blood and Marrow Transplantation, Department of Medicine., Pan Y; Division of Blood and Marrow Transplantation, Department of Medicine., Baker J; Division of Blood and Marrow Transplantation, Department of Medicine., Buechele C; Department of Pathology, and., Luong RH; Department of Comparative Medicine, Stanford University, Stanford, CA., Meyer EH; Division of Blood and Marrow Transplantation, Department of Medicine., Negrin RS; Division of Blood and Marrow Transplantation, Department of Medicine.
Jazyk:	angličtina
Zdroj:	Blood [Blood] 2014 Nov 20; Vol. 124 (22), pp. 3320-8. Date of Electronic Publication: 2014 Oct 07.
DOI:	10.1182/blood-2014-05-576017
Abstrakt:	Dysregulated donor T cells lead to destruction of host tissues resulting in graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT). We investigated the impact of highly purified (>95%) donor CD4(+) invariant natural killer T (iNKT) cells on GVHD in a murine model of allogeneic HCT. We found that low doses of adoptively transferred donor CD4(+) iNKT cells protect from GVHD morbidity and mortality through an expansion of donor CD4(+)CD25(+)FoxP3(+) regulatory T cells (Tregs). These Tregs express high levels of the Ikaros transcription factor Helios and expand from the Treg pool of the donor graft. Furthermore, CD4(+) iNKT cells preserve T-cell-mediated graft-versus-tumor effects. Our studies reveal new aspects of the cellular interplay between iNKT cells and Tregs in the context of tolerance induction after allogeneic HCT and set the stage for clinical translation. (© 2014 by The American Society of Hematology.)
Databáze:	MEDLINE
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