Selective reduction of graft-versus-host disease-mediating human T cells by ex vivo treatment with soluble Fas ligand

Osnat Bohana-Kashtan, Sebastien Morisot, Richard Hildreth, Cory Brayton, Hyam I. Levitsky, Curt I. Civin

Research output: Contribution to journalArticle

Abstract

Previous work done in our laboratory, using mouse models, showed that soluble Fas ligand (sFasL) can efficiently delete donor anti-host T cells during their activation against irradiated host cells in MLCs. In the mouse models, this ex vivo sFasL treatment abrogated graft-vs-host disease (GVHD) while sparing donor T cells with antitumor reactivity. The present work was performed with human cells, to extend our work toward reduction of clinical GVHD. PBMC responders from a given individual (first party) were stimulated in vitro with irradiated PBMC stimulators from a second person (second party), in the presence of sFasL. In control MLCs without sFasL, alloreacting T cells began to up-regulate Fas (CD95) detectably and became sensitive to Fas-mediated apoptosis by as early as day 1-2. In MLCs containing sFasL, there were greatly reduced numbers of alloreacting CD3+CFSElo cells, activation Ag-expressing CD4hi and CD8hi cells, IFN-γ-producing CD4+ and CD8+ cells, and CD8+CD107a + CTLs. Furthermore, mice transplanted with the ex vivo sFasL/MLR-treated cells had prolonged time to fatal GVHD in an in vivo xenogeneic GVHD model. Responder cells harvested from primary MLCs containing sFasL had reduced proliferation in response to second party cells, but proliferated in response to CMV Ags, PHA, and third party cells. In addition, sFasL/MLR-treated cell populations contained influenza-specific T cells, CD4+FOXP3+ T cells, and CD4+CD25+ T cells. These data indicate that this ex vivo sFasL/MLR depletion of alloreacting human donor anti-host T cells was efficient and selective.

Original languageEnglish (US)
Pages (from-to)696-705
Number of pages10
JournalJournal of Immunology
Volume183
Issue number1
DOIs
StatePublished - Jul 1 2009

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Fas Ligand Protein
Graft vs Host Disease
T-Lymphocytes
Human Influenza
Up-Regulation
Apoptosis

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

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Selective reduction of graft-versus-host disease-mediating human T cells by ex vivo treatment with soluble Fas ligand. / Bohana-Kashtan, Osnat; Morisot, Sebastien; Hildreth, Richard; Brayton, Cory; Levitsky, Hyam I.; Civin, Curt I.

In: Journal of Immunology, Vol. 183, No. 1, 01.07.2009, p. 696-705.

Research output: Contribution to journalArticle

Bohana-Kashtan, Osnat ; Morisot, Sebastien ; Hildreth, Richard ; Brayton, Cory ; Levitsky, Hyam I. ; Civin, Curt I. / Selective reduction of graft-versus-host disease-mediating human T cells by ex vivo treatment with soluble Fas ligand. In: Journal of Immunology. 2009 ; Vol. 183, No. 1. pp. 696-705.
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