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Donor T cell–derived TNF is required for graft-versus-host disease and graft-versus-tumor activity after bone marrow transplantation
| Content Provider | Scilit |
|---|---|
| Author | Schmaltz, Cornelius Alpdogan, Onder Muriglan, Stephanie J. Kappel, Barry J. Rotolo, Jimmy A. Ricchetti, Eric T. Greenberg, Andrew S. Willis, Lucy M. Murphy, George F. Crawford, James M. Brink, Marcel R. M. Van Den Brun, Ann C. M. Bjornsson, Jon Mar Magnusson, Mattias Larsson, Nina Levéen, Per Ehinger, Mats Nilsson, Eva Karlsson, Stefan |
| Copyright Year | 2003 |
| Description | Previous studies in murine bone marrow transplantation (BMT) models using neutralizing anti-tumor necrosis factor (TNF) antibodies or TNF receptor (TNFR)–deficient recipients have demonstrated that TNF can be involved in both graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL). TNF in these GVHD and GVL models was thought to be primarily produced by activated monocytes and macrophages, and the role of T cell–derived TNF was not determined. We used TNF−/− mice to study the specific role of TNF produced by donor T cells in a well-established parent-into-F1 hybrid model (C57BL/6J→C3FeB6F1/J). Recipients of TNF−/− T cells developed significantly less morbidity and mortality from GVHD than recipients of wild-type (wt) T cells. Histology of GVHD target organs revealed significantly less damage in thymus, small bowel, and large bowel, but not in liver or skin tissues from recipients of TNF−/− T cells. Recipients of TNF−/−T cells which were also inoculated with leukemia cells at the time of BMT showed increased mortality from leukemia when compared with recipients of wt cells. We found that TNF−/− T cells do not have intrinsic defects in vitro or in vivo in proliferation, IFN-γ production, or alloactivation. We could not detect TNF in the serum of our transplant recipients, suggesting that T cells contribute to GVHD and GVL via membrane-bound or locally released TNF. |
| Related Links | http://www.bloodjournal.org/content/bloodjournal/101/6/2440.full.pdf |
| Ending Page | 2445 |
| Page Count | 6 |
| Starting Page | 2440 |
| DOI | 10.1182/blood-2002-07-2109 |
| Journal | Blood |
| Issue Number | 6 |
| Volume Number | 101 |
| Language | English |
| Publisher | American Society of Hematology |
| Publisher Date | 2003-03-15 |
| Access Restriction | Open |
| Subject Keyword | Research and Experimental Medicine Bone Marrow Transplantation Gvhd Tnf Receptor Mortality Macrophages Gvl Histology Hybrid Model Journal: Blood (Vol- 90, Issue- 6) |
| Content Type | Text |
| Resource Type | Article |
