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


Authors: Borsotti, C.; Franklin, A. R. K.; Lu, S. X.; Kim, T. D.; Smith, O. M.; Suh, D.; King, C. G.; Chow, A.; Liu, C.; Alpdogan, O.; van den Brink, M. R. M.
Article 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-α 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 Δ/Δ) 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. © 2007 by The American Society of Hematology.
Keywords: controlled study; protein expression; nonhuman; comparative study; protein function; cell proliferation; t lymphocyte; t-lymphocytes; animal cell; mouse; animals; mice; animal experiment; animal model; allogenic bone marrow transplantation; cytotoxicity; cell line, tumor; mice, inbred balb c; mice, inbred strains; graft versus host reaction; protein secretion; bone marrow transplantation; graft vs host disease; cell activation; graft versus leukemia effect; tumor necrosis factor; mastocytoma; lymphocyte transfusion; graft vs host reaction; mice, inbred dba
Journal Title: Blood
Volume: 110
Issue: 2
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2007-07-15
Start Page: 783
End Page: 786
Language: English
DOI: 10.1182/blood-2006-10-054510
PUBMED: 17395784
PROVIDER: scopus
PMCID: PMC1924485
DOI/URL:
Notes: --- - "Cited By (since 1996): 13" - "Export Date: 17 November 2011" - "CODEN: BLOOA" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Theo Daniel Kim
    14 Kim
  2. Christopher King
    29 King
  3. Sydney X Lu
    51 Lu
  4. Odette Marsinay Smith
    95 Smith
  5. David Suh
    41 Suh