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Absence of donor T-cell-derived soluble TNF decreases graft-versus-host disease without impairing graft-versus-tumor activity.
- Source :
-
Blood [Blood] 2007 Jul 15; Vol. 110 (2), pp. 783-6. Date of Electronic Publication: 2007 Mar 29. - Publication Year :
- 2007
-
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.
- Subjects :
- Animals
Cell Line, Tumor
Graft vs Host Disease prevention & control
Lymphocyte Transfusion
Mice
Mice, Inbred BALB C
Mice, Inbred DBA
Mice, Inbred Strains
Bone Marrow Transplantation immunology
Graft vs Host Disease immunology
Graft vs Host Reaction immunology
Mastocytoma immunology
T-Lymphocytes immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0006-4971
- Volume :
- 110
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 17395784
- Full Text :
- https://doi.org/10.1182/blood-2006-10-054510