Specifically differentiated T cell subset promotes tumor immunity over fatal immunity

J Exp Med. 2017 Dec 4;214(12):3577-3596. doi: 10.1084/jem.20170041. Epub 2017 Oct 16.


Allogeneic immune cells, particularly T cells in donor grafts, recognize and eliminate leukemic cells via graft-versus-leukemia (GVL) reactivity, and transfer of these cells is often used for high-risk hematological malignancies, including acute myeloid leukemia. Unfortunately, these cells also attack host normal tissues through the often fatal graft-versus-host disease (GVHD). Full separation of GVL activity from GVHD has yet to be achieved. Here, we show that, in mice and humans, a population of interleukin-9 (IL-9)-producing T cells activated via the ST2-IL-33 pathway (T9IL-33 cells) increases GVL while decreasing GVHD through two opposing mechanisms: protection from fatal immunity by amphiregulin expression and augmentation of antileukemic activity compared with T9, T1, and unmanipulated T cells through CD8α expression. Thus, adoptive transfer of allogeneic T9IL-33 cells offers an attractive approach for separating GVL activity from GVHD.

MeSH terms

  • Adoptive Transfer
  • Amphiregulin / metabolism
  • Animals
  • Cell Communication
  • Cell Differentiation / immunology*
  • Cell Line
  • Cell Line, Tumor
  • Cytotoxicity, Immunologic
  • Epithelial Cells / metabolism
  • Graft vs Host Disease / pathology
  • Humans
  • Immunity*
  • Immunologic Memory
  • Interleukin-1 Receptor-Like 1 Protein / metabolism
  • Interleukin-33 / metabolism
  • Interleukin-9 / metabolism
  • Intestines / pathology
  • Leukemia / immunology
  • Leukemia / pathology
  • Mice, Inbred BALB C
  • Phenotype
  • Proto-Oncogene Proteins / metabolism
  • Signal Transduction
  • Survival Analysis
  • T-Lymphocyte Subsets / cytology*
  • T-Lymphocyte Subsets / immunology*
  • Trans-Activators / metabolism


  • Amphiregulin
  • Il1rl1 protein, mouse
  • Interleukin-1 Receptor-Like 1 Protein
  • Interleukin-33
  • Interleukin-9
  • Proto-Oncogene Proteins
  • Trans-Activators
  • proto-oncogene protein Spi-1