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, James L M Ferrara

Research output: Contribution to journalArticle

Abstract

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 (H2 b/d) or allogeneic B6 (H2 b) 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.

Original languageEnglish (US)
Pages (from-to)3429-3431
Number of pages3
JournalBlood
Volume100
Issue number9
DOIs
StatePublished - Nov 1 2002
Externally publishedYes

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Transplantation (surgical)
Perforin
Interleukin-18
Homologous Transplantation
Bone Marrow Transplantation
Grafts
Bone
Leukemia
Transplants
T-cells
Graft vs Host Disease
T-Lymphocytes
Bone Marrow
Tissue Donors
Mastocytoma
Animals
Mortality
Therapeutics

ASJC Scopus subject areas

  • Hematology

Cite this

Interleukin 18 preserves a perforin-dependent graft-versus-leukemia effect after allogeneic bone marrow transplantation. / Reddy, Pavan; Teshima, Takanori; Hildebrandt, Gerhard; Duffner, Ulrich; Maeda, Yoshinobu; Cooke, Kenneth R; Ferrara, James L M.

In: Blood, Vol. 100, No. 9, 01.11.2002, p. 3429-3431.

Research output: Contribution to journalArticle

Reddy, P, Teshima, T, Hildebrandt, G, Duffner, U, Maeda, Y, Cooke, KR & Ferrara, JLM 2002, 'Interleukin 18 preserves a perforin-dependent graft-versus-leukemia effect after allogeneic bone marrow transplantation', Blood, vol. 100, no. 9, pp. 3429-3431. https://doi.org/10.1182/blood-2002-04-1252
Reddy, Pavan ; Teshima, Takanori ; Hildebrandt, Gerhard ; Duffner, Ulrich ; Maeda, Yoshinobu ; Cooke, Kenneth R ; Ferrara, James L M. / Interleukin 18 preserves a perforin-dependent graft-versus-leukemia effect after allogeneic bone marrow transplantation. In: Blood. 2002 ; Vol. 100, No. 9. pp. 3429-3431.
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