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Blood, 15 July 2007, Vol. 110, No. 2, pp. 783-786.
Prepublished online as a Blood First Edition Paper on March 29, 2007; DOI 10.1182/blood-2006-10-054510.
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TRANSPLANTATION
Brief Report
Absence of donor T-cellderived soluble TNF decreases graft-versus-host disease without impairing graft-versus-tumor activity
Chiara Borsotti1,
Anna R. K. Franklin1,
Sydney X. Lu1,
Theo D. Kim1,
Odette M. Smith1,
David Suh1,
Chris G. King1,
Andrew Chow1,
Chen Liu2,
Onder Alpdogan1, and
Marcel R. M. van den Brink1
1 Departments of Medicine and Immunology, Memorial Sloan-Kettering Cancer Center, New York, NY;
2 Department of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine, Gainesville
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- converting enzyme (TACE). To study the contribution of donor T-cellderived memTNF versus solTNF in GVHD and GVT, we used mice containing a noncleavable allele in place of endogenous TNF (memTNF / ) 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.

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