title: Absence of donor T-cell-derived soluble TNF decreases graft-versus-host disease without impairing graft-versus-tumor activity.
abstract: Tumor necrosis factor (TNF) plays an important role in graft-versus-host disease (GVHD) and graft-versus-tumor (GVT) activity after allogeneic bone marrow transplantation (allo-BMT). TNF can be expressed in a membrane-bound form (memTNF) and as a soluble (solTNF) molecule after being cleaved by the TNF-alpha converting enzyme (TACE). To study the contribution of donor T-cell-derived memTNF versus solTNF in GVHD and GVT, we used mice containing a noncleavable allele in place of endogenous TNF (memTNF(Delta/Delta)) as donors in murine BMT models. Recipients of memTNF T cells developed significantly less GVHD than recipients of wild-type (wt) T cells. In contrast, GVT activity mediated by memTNF T cells remained intact, and alloreactive memTNF T cells showed no defects in proliferation, activation, and cytotoxicity. These data suggest that suppressing the secretion of solTNF by donor T cells significantly decreases GVHD without impairing GVT activity.
authors: Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors: Chiara
authors: C
authors: Borsotti
authors: Anna R K
authors: AR
authors: Franklin
authors: Sydney X
authors: SX
authors: Lu
authors: Theo D
authors: TD
authors: Kim
authors: Odette M
authors: OM
authors: Smith
authors: David
authors: D
authors: Suh
authors: Chris G
authors: CG
authors: King
authors: Andrew
authors: A
authors: Chow
authors: Chen
authors: C
authors: Liu
authors: Onder
authors: O
authors: Alpdogan
authors: Marcel R M
authors: MR
authors: van den Brink
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology*; D045744:Cell Line, Tumor; D006086:Graft vs Host Disease / Q000276:immunology* / Q000517:prevention & control; D006087:Graft vs Host Reaction / Q000276:immunology*; D017710:Lymphocyte Transfusion; D034801:Mastocytoma / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D013601:T-Lymphocytes / Q000276:immunology*