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Influence of cell dose and graft-versus-host reactivity on rejection rates
after allogeneic bone marrow transplantation
L Uharek, W Gassmann, B Glass, J Steinmann, H Loeffler and W Mueller-Ruchholtz
Department of Immunology, University of Kiel, Germany.
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.
Volume 79,
Issue 6,
pp. 1612-1621,
03/15/1992
Copyright © 1992 by The American Society of Hematology
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