IL-11 separates graft-versus-leukemia effects from graft-versus-host disease after bone marrow transplantation

Takanori Teshima, Geoffrey R. Hill, Luying Pan, Yani S. Brinson, Marcel R.M. Van Den Brink, Kenneth R. Cooke, James L.M. Ferrara

Research output: Contribution to journalArticlepeer-review

Abstract

We recently showed that IL-11 prevents lethal graft-versus-host disease (GVHD) in a murine bone marrow transplantation (BMT) model of GVHD directed against MHC and minor antigens. In this study, we have investigated whether IL-11 can maintain a graft-versus-leukemia (GVL) effect. Lethally irradiated B6D2F1 mice were transplanted with either T cell-depleted (TCD) bone marrow (BM) alone or with BM and splenic T cells from allogeneic B6 donors. Animals also received host-type P815 mastocytoma cells at the time of BMT. Recipients were injected subcutaneously with recombinant human IL-11 or control diluent twice daily, from 2 days before BMT to 7 days after BMT. TCD recipients all died from leukemia by day 23. All control- and IL-11-treated allogeneic animals effectively rejected their leukemia, but IL-11 also reduced GVHD- related mortality. Examination of the cellular mechanisms of GVL and GVHD in this system showed that IL-11 selectively inhibited CD4-mediated GVHD, while retaining both CD4- and CD8-mediated GVL. In addition, IL-11 treatment did not affect cytolytic effector functions oft cells after BMT either in vivo or in vitro. Studies with perforin-deficient donor T cells demonstrated that the GVL effect was perforin dependent. These data demonstrated that IL-11 can significantly reduce CD4-dependent GVHD without impairing cytolytic function or subsequent GVL activity of CD8 T cells. Brief treatment with IL-11 shortly after BMT may therefore represent a novel strategy for separating GVHD and GVL.

Original languageEnglish (US)
Pages (from-to)317-325
Number of pages9
JournalJournal of Clinical Investigation
Volume104
Issue number3
DOIs
StatePublished - Aug 1999
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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