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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.

SUBMITTER: Borsotti C 

PROVIDER: S-EPMC1924485 | biostudies-other | 2007 Jul

REPOSITORIES: biostudies-other

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

Borsotti Chiara C   Franklin Anna R K AR   Lu Sydney X SX   Kim Theo D TD   Smith Odette M OM   Suh David D   King Chris G CG   Chow Andrew A   Liu Chen C   Alpdogan Onder O   van den Brink Marcel R M MR  

Blood 20070329 2


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 (me  ...[more]

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