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WR Gerritsen and RJ O'Reilly
Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York,
NY.
The major immunological reactions after an allogeneic bone marrow
transplantation (BMT) are graft rejection and graft-versus-host disease
(GVHD). GVHD can be prevented by T-cell depletion of the allogeneic BM
graft, but the beneficial effect of T-cell depletion on the incidence of
GVHD is counterbalanced by a higher incidence of graft failure. One option
for the prevention of graft rejection after T-cell-depleted BM grafts is
the administration of cytokines. Before applying cytokines after an
allogeneic BMT, we considered it desirable to learn whether cytokines would
alter the susceptibility of donor BM cells to host T cells. An in vitro
assay was developed to investigate the role of the cytokines interleukin-1
(IL-1), IL-3, granulocyte colony-stimulating factor (G-CSF) and
granulocyte-macrophage CSF (GM-CSF) on the interaction between
allosensitized, cytotoxic-T cells (CTLs) and T-cell- depleted BM cells.
CTLs primed against the BM donor suppressed the formation of colonies
consisting of granulocytes and macrophages (colony-forming unit GM). Colony
formation was not inhibited by CTLs sensitized against a third party.
Accordingly, the number of colonies scored in cocultures with CTLs
sensitized to third party antigens were designated as 0% inhibition. A 66%
inhibition of colony formation was observed for untreated BM cells at an
effector:target (E:T) ratio of 1:1. Pretreatment of the BM cells with the
cytokines G-CSF, GM-CSF, IL- 1, and IL-3 resulted in a 38% (P = .001), 53%,
66%, and 68% inhibition of colony formation, respectively, at E:T ratios of
1:1. G-CSF reduced the susceptibility of BM cells over a range from 4:1 to
1:16 (E:T ratios). GM-CSF had only significant influence at the lower E:T
ratios (1:4 and 1:16). These in vitro data indicate that G-CSF could
protect BM cells from killing by allosensitized CTLs and suggest that
administration of these cytokines might potentially reduce the
susceptibility of T-cell-depleted allogeneic BM grafts to host T-cell-
mediated rejection.
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| Copyright © 1994 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||