Third-party CD4+ invariant natural killer T cells protect from murine GVHD lethality.

Autor:	Schneidawind D; Division of Blood and Marrow Transplantation, Department of Medicine., Baker J; Division of Blood and Marrow Transplantation, Department of Medicine., Pierini A; 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] 2015 May 28; Vol. 125 (22), pp. 3491-500. Date of Electronic Publication: 2015 Mar 20.
DOI:	10.1182/blood-2014-11-612762
Abstrakt:	Graft-versus-host disease (GVHD) is driven by extensive activation and proliferation of alloreactive donor T cells causing significant morbidity and mortality following allogeneic hematopoietic cell transplantation (HCT). Invariant natural killer T (iNKT) cells are a potent immunoregulatory T-cell subset in both humans and mice. Here, we explored the role of adoptively transferred third-party CD4(+) iNKT cells for protection from lethal GVHD in a murine model of allogeneic HCT across major histocompatibility barriers. We found that low numbers of CD4(+) iNKT cells from third-party mice resulted in a significant survival benefit with retained graft-versus-tumor effects. In vivo expansion of alloreactive T cells was diminished while displaying a T helper cell 2-biased phenotype. Notably, CD4(+) iNKT cells from third-party mice were as protective as CD4(+) iNKT cells from donor mice although third-party CD4(+) iNKT cells were rejected early after allogeneic HCT. Adoptive transfer of third-party CD4(+) iNKT cells resulted in a robust expansion of donor CD4(+)CD25(+)FoxP3(+) regulatory T cells (Tregs) that were required for protection from lethal GVHD. However, in vivo depletion of myeloid-derived suppressor cells abrogated both Treg expansion and protection from lethal GVHD. Despite the fact that iNKT cells are a rare cell population, the almost unlimited third-party availability and feasibility of in vitro expansion provide the basis for clinical translation. (© 2015 by The American Society of Hematology.)
Databáze:	MEDLINE
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