Donor T cell-derived TNF is required for graft-versus-host disease and graft-versus-tumor activity after bone marrow transplantation Journal Article


Authors: Schmaltz, C.; Alpdogan, O.; Muriglan, S. J.; Kappel, B. J.; Rotolo, J. A.; Ricchetti, E. T.; Greenberg, A. S.; Willis, L. M.; Murphy, G. F.; Crawford, J. M.; van den Brink, M. R. M.
Article Title: Donor T cell-derived TNF is required for graft-versus-host disease and graft-versus-tumor activity after bone marrow transplantation
Abstract: 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-/- mica 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. © 2003 by The American Society of Hematology.
Keywords: controlled study; mortality; nonhuman; protein function; t lymphocyte; t-lymphocytes; animal cell; mouse; animals; mice; mice, knockout; morbidity; animal experiment; mice, inbred c57bl; cancer mortality; liver; tissue donors; tumor necrosis factor-alpha; thymus; thymus gland; leukemia cell; cd4-positive t-lymphocytes; graft versus host reaction; cytokine production; tumor necrosis factor receptor; intestine, large; neoplasm transplantation; bone marrow transplantation; graft vs host disease; small intestine; intestine, small; cell activation; cell adhesion; membrane binding; tumor necrosis factor; mice, inbred c3h; graft vs leukemia effect; large intestine; female; priority journal; article; leukemia, experimental
Journal Title: Blood
Volume: 101
Issue: 6
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2003-03-15
Start Page: 2440
End Page: 2445
Language: English
DOI: 10.1182/blood-2002-07-2109
PUBMED: 12424195
PROVIDER: scopus
DOI/URL:
Notes: Export Date: 12 September 2014 -- Source: Scopus
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MSK Authors
  1. Jimmy A Rotolo
    31 Rotolo
  2. Lucy Willis
    27 Willis
  3. Barry J Kappel
    28 Kappel