Absence of donor T-cell-derived soluble TNF decreases graft-versus-host disease without impairing graft-versus-tumor activity Academic Article uri icon

Overview

MeSH Major

  • Bone Marrow Transplantation
  • Graft vs Host Disease
  • Graft vs Host Reaction
  • Mastocytoma
  • T-Lymphocytes

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.

publication date

  • July 15, 2007

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC1924485

Digital Object Identifier (DOI)

  • 10.1182/blood-2006-10-054510

PubMed ID

  • 17395784

Additional Document Info

start page

  • 783

end page

  • 6

volume

  • 110

number

  • 2