Journal article
Tim-3 is an inducible human natural killer cell receptor that enhances interferon gamma production in response to galectin-9
Blood, Vol.119(13), pp.3064-3072
03/29/2012
DOI: 10.1182/blood-2011-06-360321
PMCID: PMC3321868
PMID: 22323453
Abstract
NK-cell function is regulated by the integration of signals received from activating and inhibitory receptors. Here we show that a novel immune receptor, T-cell Ig and mucin-containing domain-3 (Tim-3), is expressed on resting human NK cells and is up-regulated on activation. The NK92 NK-cell line engineered to overexpress Tim-3 showed a marked increase in IFN-γ production in the presence of soluble rhGal-9 or Raji tumor cells engineered to express Gal-9. The Tim-3
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population of low-dose IL-12/IL-18–activated primary NK cells significantly increased IFN-γ production in response to soluble rhGal-9, Gal-9 presented by cell lines, and primary acute myelogenous leukemia (AML) targets that endogenously express Gal-9. This effect is highly specific as Tim-3 Ab blockade significantly decreased IFN-γ production, and Tim-3 cross-linking induced ERK activation and degradation of IκBα. Exposure to Gal-9–expressing target cells had little effect on CD107a degranulation. Reconstituted NK cells obtained from patients after hematopoietic cell transplantation had diminished expression of Tim-3 compared with paired donors. This observation correlates with the known IFN-γ defect seen early posttransplantation. In conclusion, we show that Tim-3 functions as a human NK-cell coreceptor to enhance IFN-γ production, which has important implications for control of infectious disease and cancer.
Details
- Title: Subtitle
- Tim-3 is an inducible human natural killer cell receptor that enhances interferon gamma production in response to galectin-9
- Creators
- Michelle K Gleason - Adult andTodd R Lenvik - Adult andValarie McCullar - Adult andMartin Felices - Adult andM. Shea O'Brien - Adult andSarah A Cooley - Adult andMichael R Verneris - Pediatric Divisions of Hematology, Oncology and Transplantation, University of Minnesota Cancer Center, Minneapolis, MNFrank Cichocki - Adult andCarol J Holman - Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN; andAngela Panoskaltsis-Mortari - Pediatric Divisions of Hematology, Oncology and Transplantation, University of Minnesota Cancer Center, Minneapolis, MNToshiro Niki - Department of Immunology & Immunopathology, Faculty of Medicine, Kagawa University, Kagawa, JapanMitsuomi Hirashima - Department of Immunology & Immunopathology, Faculty of Medicine, Kagawa University, Kagawa, JapanBruce R Blazar - Pediatric Divisions of Hematology, Oncology and Transplantation, University of Minnesota Cancer Center, Minneapolis, MNJeffrey S Miller - Adult and
- Resource Type
- Journal article
- Publication Details
- Blood, Vol.119(13), pp.3064-3072
- Publisher
- American Society of Hematology; Washington, DC
- DOI
- 10.1182/blood-2011-06-360321
- PMID
- 22323453
- PMCID
- PMC3321868
- ISSN
- 0006-4971
- eISSN
- 1528-0020
- Grant note
- P01-CA111412-01; R01 HL55417; R01 CA72669 / National Institutes of Health
- Language
- English
- Date published
- 03/29/2012
- Academic Unit
- Pathology
- Record Identifier
- 9984046902102771
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