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:	http://www.scopus.com/inward/record.url?eid=2-s2.0-34547103280&partnerID=40&md5=98b0a72459799602dd59c790c13bb340
Notes:	--- - "Cited By (since 1996): 13" - "Export Date: 17 November 2011" - "CODEN: BLOOA" - "Source: Scopus"

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