THE EFFECT OF DONOR LYMPHOCYTES-T AND TOTAL-BODY IRRADIATION ON HEMATOPOIETIC ENGRAFTMENT AND PULMONARY TOXICITY FOLLOWING EXPERIMENTAL ALLOGENEIC BONE-MARROW TRANSPLANTATION

被引:45
作者
DOWN, JD
MAUCH, P
WARHOL, M
NEBEN, S
FERRARA, JLM
机构
[1] HARVARD UNIV, SCH MED, JOINT CTR RADIAT THERAPY, BOSTON, MA 02115 USA
[2] HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DIV PEDIAT ONCOL, BOSTON, MA 02115 USA
[3] CHILDRENS HOSP MED CTR, BOSTON, MA 02115 USA
[4] PENN HOSP, DEPT PATHOL, PHILADELPHIA, PA 19107 USA
关键词
D O I
10.1097/00007890-199211000-00007
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
To study the effects of donor T lymphocytes on engraftment and graft-versus-host disease in relation to recipient total-body irradiation, we have returned small numbers of T cells to T-cell-depleted bone marrow transplanted across a minor histocompatibility barrier in mice (B10.BR --> CBA). T-cell-depleted B10.BR marrow (10(7) cells) was transplanted into CBA recipients prepared with TBI doses ranging from 4 to 14 Gy. Selected animals also received 10(4) (0.1%) and 10(5) (1.0%) measured B10.BR T lymphocytes. The extent of donor marrow engraftment was determined from hemoglobin and carbonic anhydrase phenotyping of peripheral blood at 3 months posttransplant. Toxicity was assessed from breathing-rate measurements, histopathology, and animal survival. Addition of T cells had a profound effect on survival related to radiation dose. The TBI doses resulting in an LD50 at 12 weeks were 6.9 Gy, 9.3 Gy, and 13.0 Gy for animals receiving 10(5), 10(4), and no T cells, respectively. Mortality was associated with pulmonary dysfunction as measured by an elevation of breathing rates. Autopsy and histological analysis revealed extensive damage to the lung parenchyma. In contrast to the toxicity data, addition of T cells to the donor marrow had no effect on the TBI dose required for equivalent erythroid engraftment. These results demonstrate that in combination with TBI small numbers of T cells in the transplanted marrow do not aid engraftment but do significantly increase the risk of pulmonary toxicity.
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页码:802 / 808
页数:7
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