THE EFFECT OF PRETREATMENT OF ALLOGENEIC BONE MARROW GRAFT RECIPIENTS WITH ANTILYMPHOCYTIC SERUM ON THE ACUTE GRAFT-VERSUS-HOST REACTION IN MONKEYS

1972 ◽  
Vol 13 (4) ◽  
pp. 400-407 ◽  
Author(s):  
D W van Bekkum ◽  
H Balner ◽  
K A Dicke ◽  
F G Van Den Berg ◽  
G H Prinsen ◽  
...  
1982 ◽  
Vol 33 (2) ◽  
pp. 168-173 ◽  
Author(s):  
KERRY ATKINSON ◽  
RAINER STORB ◽  
HANS D. OCHS ◽  
SONDRA GOEHLE ◽  
KEITH M. SULLIVAN ◽  
...  

Blood ◽  
1992 ◽  
Vol 79 (6) ◽  
pp. 1612-1621 ◽  
Author(s):  
L Uharek ◽  
W Gassmann ◽  
B Glass ◽  
J Steinmann ◽  
H Loeffler ◽  
...  

Abstract The number of cells transplanted and their capacity to induce graft- versus-host reactivity (GvHR) are two factors that are suspected to influence the engraftment of allogeneic bone marrow. We have investigated their impact on graft rejection rates in busulfan-treated LEW rats. In a series of experiments, we varied (1) the number of marrow cells transferred (1, 5, 10, 20, 30, and 40 x 10(7)), (2) the degree of pretransplant immunosuppression (1.5, 3.0, and 4.5 Gy of total body irradiation [TBI]; 0, 30, 60, 90, 120, and 180 mg/kg cyclophosphamide), and (3) the ability of the marrow graft to induce classical GvHR against major histocompatibility complex (MHC) antigens [semiallogeneic (CAP x LEW)F1 or CAP rats as marrow donors]. Reducing either the immunosuppressive pretreatment or the number of cells transplanted resulted in a stepwise increase in rejection rates. However, every reduction in the size of the marrow inoculum was compensated by increased immunosuppression and vice versa. While 60 mg/kg cyclophosphamide was sufficient to prevent rejections after grafting of 40 x 10(7) cells, 90 mg/kg was necessary to ensure 100% engraftment after transplantation of 20 x 10(7) cells, 120 mg/kg after 10 x 10(7) cells, and 180 mg/kg after 1 x 10(7) cells. Since CAP marrow leads to GvHR-mediated immunosuppression in LEW recipients, in contrast to (CAP x LEW)F1 marrow, we had supposed that lower cell numbers or cyclophosphamide doses are sufficient to achieve engraftment of CAP marrow. Although severe GvHR was present in all animals receiving escalating doses of CAP cells, the rejection rates were the same as for (CAP x LEW)F1 marrow. In conclusion, we have demonstrated that there is a sensitive balance between the immunosuppression of the host and the number of marrow cells transferred. We were not able to number of marrow cells transferred. We were not able to detect a beneficial effect of classical GvHR against MHC antigens on the engraftment of allogeneic marrow. Thus, our results do not support the hypothesis that the loss of GvHR-mediated immunosuppression is responsible for higher rejection rates following transplantation of T-cell-depleted bone marrow.


1987 ◽  
Vol 42 (4) ◽  
pp. 461-464 ◽  
Author(s):  
Irmgard Ziegler ◽  
Stefan Thierfelder

Abstract Normal engraftment of bone marrow transplants depends on histocompatibility between donor and recipient. In this case reconstitution of hemopoiesis and lymphopoiesis in the mouse spleen is correlated with transient biopterin synthesis in these cells. Allogeneic bone marrow progeny cells undergo donor cell proliferation in the spleen prior to the incidence of graft-versus-host reaction. These cells are not committed to biopterin synthesis. Thy-1 monoclonal antibody fully repairs engraftment of allogeneic transplants together with biopterin synthesis.


Blood ◽  
1992 ◽  
Vol 79 (6) ◽  
pp. 1612-1621 ◽  
Author(s):  
L Uharek ◽  
W Gassmann ◽  
B Glass ◽  
J Steinmann ◽  
H Loeffler ◽  
...  

The number of cells transplanted and their capacity to induce graft- versus-host reactivity (GvHR) are two factors that are suspected to influence the engraftment of allogeneic bone marrow. We have investigated their impact on graft rejection rates in busulfan-treated LEW rats. In a series of experiments, we varied (1) the number of marrow cells transferred (1, 5, 10, 20, 30, and 40 x 10(7)), (2) the degree of pretransplant immunosuppression (1.5, 3.0, and 4.5 Gy of total body irradiation [TBI]; 0, 30, 60, 90, 120, and 180 mg/kg cyclophosphamide), and (3) the ability of the marrow graft to induce classical GvHR against major histocompatibility complex (MHC) antigens [semiallogeneic (CAP x LEW)F1 or CAP rats as marrow donors]. Reducing either the immunosuppressive pretreatment or the number of cells transplanted resulted in a stepwise increase in rejection rates. However, every reduction in the size of the marrow inoculum was compensated by increased immunosuppression and vice versa. While 60 mg/kg cyclophosphamide was sufficient to prevent rejections after grafting of 40 x 10(7) cells, 90 mg/kg was necessary to ensure 100% engraftment after transplantation of 20 x 10(7) cells, 120 mg/kg after 10 x 10(7) cells, and 180 mg/kg after 1 x 10(7) cells. Since CAP marrow leads to GvHR-mediated immunosuppression in LEW recipients, in contrast to (CAP x LEW)F1 marrow, we had supposed that lower cell numbers or cyclophosphamide doses are sufficient to achieve engraftment of CAP marrow. Although severe GvHR was present in all animals receiving escalating doses of CAP cells, the rejection rates were the same as for (CAP x LEW)F1 marrow. In conclusion, we have demonstrated that there is a sensitive balance between the immunosuppression of the host and the number of marrow cells transferred. We were not able to number of marrow cells transferred. We were not able to detect a beneficial effect of classical GvHR against MHC antigens on the engraftment of allogeneic marrow. Thus, our results do not support the hypothesis that the loss of GvHR-mediated immunosuppression is responsible for higher rejection rates following transplantation of T-cell-depleted bone marrow.


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