Brief ex vivo Fas-ligand incubation attenuates GvHD without compromising stem cell graft performance

Hilit Levy-Barazany, Liat Shachnai-Pinkas, Galina Rodionov, Alex Saar, Michal Rosenzwaig, Liron Gez, Anastasia Rodin, Nitzan Marelly, Michal Abraham, Inbal Mishalian, Hila Wildbaum, Tamar Katz, Yuval Baar, Shai Yarkoni*, Ronit Bakimer-Kleiner, Amnon Peled, Tsila Zuckerman, Jerry Stein

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Graft versus host disease (GvHD) remains a limiting factor for successful hematopoietic stem cell transplantation (HSCT). T cells and antigen-presenting cells (APCs) are major components of the hematopoietic G-CSF mobilized peripheral blood cell (MPBC) graft. Here we show that a short incubation (2 h) of MPBCs with hexameric Fas ligand (FasL) selectively induces apoptosis of specific donor T cell subsets and APCs but not of CD34+ cells. FasL treatment preferentially induces apoptosis in mature T cell subsets which express high levels of Fas (CD95), such as T stem cell memory, T central memory, and T effector memory cells, as well as TH1 and TH17 cells. Anti-CD3/CD28 stimulated T cells derived from FasL-treated-MPBCs express lower levels of CD25 and secrete lower levels of IFN-γ as compared to control cells not treated with FasL. FasL treatment also induces apoptosis of transitional, naïve, memory and plasmablastoid B cells leading to a reduction in their numbers in the graft and following engraftment in transplanted mice. Most importantly, ex vivo treatment of MPBCs with FasL prior to transplant in conditioned NOD-scid IL2Rγnull (NSG) mice prevented GvHD while preserving graft versus leukemia (GvL) effects, and leading to robust stem cell engraftment.

Original languageEnglish
Pages (from-to)1305-1316
Number of pages12
JournalBone Marrow Transplantation
Issue number7
StatePublished - 1 Jul 2020


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