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Prepublished online as a Blood First Edition Paper on July 5, 2002; DOI 10.1182/blood-2002-04-1252.
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Blood, 1 November 2002, Vol. 100, No. 9, pp. 3429-3431
BRIEF REPORT
Interleukin 18 preserves a perforin-dependent
graft-versus-leukemia effect after allogeneic bone marrow
transplantation
Pavan Reddy,
Takanori Teshima,
Gerhard Hildebrandt,
Ulrich Duffner,
Yoshinobu Maeda,
Kenneth R. Cooke, and
James L. M. Ferrara
From the Blood and Marrow Transplantation Program,
Division of Hematology-Oncology, Departments of Internal Medicine and
Pediatrics, University of Michigan Comprehensive Cancer Center, Ann
Arbor.
We have recently shown that early administration of interleukin 18 (IL-18) after bone marrow transplantation (BMT) attenuates acute
graft-versus-host disease (GVHD) in a lethally irradiated parent into
F1 (B6 B6D2F1) BMT model. In this study, we investigated whether
IL-18 can maintain graft-versus-leukemia (GVL) effect in this context.
B6D2F1 mice received transplants of T-cell-depleted (TCD) bone marrow
(BM) and splenic T cells from either syngeneic (H2b/d) or
allogeneic B6 (H2b) donors. Recipient mice were treated
with recombinant murine IL-18 or the control diluent. Initial studies
demonstrated that IL-18 treatment did not affect the proliferative
responses or the cytolytic effector functions of T cells after BMT. In
subsequent experiments, animals also received host-type P815
mastocytoma cells at the time of BMT. All syngeneic BM
transplant recipients died from leukemia by day 18. The
allogeneic BM transplant recipients effectively rejected their leukemia
regardless of treatment and IL-18 significantly reduced GVHD-related
mortality. Examination of the cytotoxic mechanisms with
perforin-deficient donor T cells demonstrated that perforin is critical
for the GVL effect. Taken together these data demonstrate that IL-18
can attenuate acute GVHD without impairing the in vitro cytolytic
function or the in vivo GVL activity after allogeneic BMT.
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