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

Specifically differentiated T cell subset promotes tumor immunity over fatal immunity.

Author information

1
Indiana University School of Medicine, Indianapolis, IN.
2
Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ.
3
Indiana University School of Medicine, Indianapolis, IN sophpacz@iu.edu.

Abstract

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.

PMID:
29038366
PMCID:
PMC5716032
DOI:
10.1084/jem.20170041
[Indexed for MEDLINE]
Free PMC Article

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