PMID- 10430613
OWN - NLM
STAT- MEDLINE
DCOM- 19990817
LR  - 20210102
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 104
IP  - 3
DP  - 1999 Aug
TI  - IL-11 separates graft-versus-leukemia effects from graft-versus-host disease
      after bone marrow transplantation.
PG  - 317-25
AB  - 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 of T 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.
FAU - Teshima, T
AU  - Teshima T
AD  - Department of Internal Medicine, University of Michigan Cancer Center, Ann Arbor 
      48109-0942, USA.
FAU - Hill, G R
AU  - Hill GR
FAU - Pan, L
AU  - Pan L
FAU - Brinson, Y S
AU  - Brinson YS
FAU - van den Brink, M R
AU  - van den Brink MR
FAU - Cooke, K R
AU  - Cooke KR
FAU - Ferrara, J L
AU  - Ferrara JL
LA  - eng
GR  - P01 CA039542/CA/NCI NIH HHS/United States
GR  - CA-39542/CA/NCI NIH HHS/United States
GR  - HL-55162/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (CD4 Antigens)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Interleukin-11)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Pore Forming Cytotoxic Proteins)
RN  - 0 (fas Receptor)
RN  - 126465-35-8 (Perforin)
SB  - IM
MH  - Animals
MH  - Bone Marrow Transplantation/adverse effects/*immunology
MH  - CD4 Antigens/physiology
MH  - CD4-Positive T-Lymphocytes/immunology
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - Cytotoxicity, Immunologic/drug effects
MH  - Disease-Free Survival
MH  - Female
MH  - Graft vs Host Disease/*immunology/prevention & control/therapy
MH  - Graft vs Tumor Effect/*immunology
MH  - Humans
MH  - Immunosuppressive Agents/therapeutic use
MH  - Interleukin-11/*physiology/therapeutic use
MH  - Leukemia, Experimental/immunology/therapy
MH  - Membrane Glycoproteins/physiology
MH  - Mice
MH  - Mice, Inbred C3H
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred DBA
MH  - Mice, Knockout
MH  - Perforin
MH  - Pore Forming Cytotoxic Proteins
MH  - Sarcoma, Experimental/immunology/therapy
MH  - T-Lymphocytes, Cytotoxic/drug effects/immunology
MH  - Tumor Cells, Cultured
MH  - fas Receptor/physiology
PMC - PMC408425
EDAT- 1999/08/03 00:00
MHDA- 1999/08/03 00:01
CRDT- 1999/08/03 00:00
PHST- 1999/08/03 00:00 [pubmed]
PHST- 1999/08/03 00:01 [medline]
PHST- 1999/08/03 00:00 [entrez]
AID - 10.1172/JCI7111 [doi]
PST - ppublish
SO  - J Clin Invest. 1999 Aug;104(3):317-25. doi: 10.1172/JCI7111.