期刊
BLOOD
卷 101, 期 6, 页码 2440-2445出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2002-07-2109
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资金
- NCI NIH HHS [P30 CA008748] Funding Source: Medline
- NHLBI NIH HHS [HL72412, HL69929] Funding Source: Medline
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. W e used TNF-1-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-/- 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-(gamma) 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.
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