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Interleukin-2 inhibits graft-versus-host disease-promoting activity of CD4+
cells while preserving CD4- and CD8-mediated graft-versus-leukemia effects
M Sykes, MW Harty, GL Szot and DA Pearson
Transplantation Biology Research Center, Massachusetts General Hospital,
Harvard Medical School, Boston 02129.
We have recently shown that a short course of high-dose interleukin-2
(IL-2) can markedly inhibit the graft-versus-host disease (GVHD)- promoting
activity of donor CD4+ T cells. The difficulty in dissociating
GVHD-promoting from graft-versus-leukemia (GVL) effects of alloreactive
donor T cells currently prevents clinical bone marrow transplantation (BMT)
from fulfilling its full potential. To test the capacity of IL-2 treatment
to promote such a dissociation, we have developed a new murine
transplantable acute myelogenous leukemia model using a class II major
histocompatibility complex-positive BALB/c Moloney murine leukemia
virus-induced promonocytic leukemia, 2B-4-2. BALB/c mice receiving 2.5 x
10(5) 2B-4-2 cells intravenously 1 week before irradiation and syngeneic
BMT died from leukemia within 2 to 4 weeks after BMT. Administration of
syngeneic spleen cells and/or a 2.5- day course of IL-2 treatment alone did
not inhibit leukemic mortality. In contrast, administration of
non-T-cell-depleted fully allogeneic B10 (H-2b) spleen cells and
T-cell-depleted B10 marrow led to a significant delay in leukemic mortality
in IL-2-treated mice. In these animals GVHD was inhibited by IL-2
treatment. GVL effects were mediated entirely by donor CD4+ and CD8+ T
cells. Remarkably, IL-2 administration did not diminish the magnitude of
the GVL effect of either T-cell subset. This was surprising, because
CD4-mediated GVHD was inhibited in the same animals in which CD4-mediated
GVL effects were not reduced by IL-2 treatment. These results suggest a
novel mechanism by which GVHD and GVL effects of a single unprimed
alloreactive T-cell subset can be dissociated; different CD4 activities
promote GVHD and GVL effects, and the former, but not the latter activities
are inhibited by treatment with IL-2.
Volume 83,
Issue 9,
pp. 2560-2569,
05/01/1994
Copyright © 1994 by The American Society of Hematology
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