Cell-Extrinsic MHC Class I Molecule Engagement Augments Human NK Cell Education Programmed by Cell-Intrinsic MHC Class I

Jeanette E. Boudreau; Xiao Rong Liu; Zeguo Zhao; Aaron Zhang; Leonard D. Shultz; Dale L. Greiner; Bo Dupont; Katharine C. Hsu

doi:10.1016/j.immuni.2016.07.005

Cell-Extrinsic MHC Class I Molecule Engagement Augments Human NK Cell Education Programmed by Cell-Intrinsic MHC Class I

Jeanette E. Boudreau, Xiao Rong Liu, Zeguo Zhao, Aaron Zhang, Leonard D. Shultz, Dale L. Greiner, Bo Dupont, Katharine C. Hsu

Producción científica: Contribución a una revista › Artículo › revisión exhaustiva

57 Citas (Scopus)

Resumen

The effector potential of NK cells is counterbalanced by their sensitivity to inhibition by “self” MHC class I molecules in a process called “education.” In humans, interactions between inhibitory killer immunoglobulin-like receptors (KIR) and human MHC (HLA) mediate NK cell education. In HLA-B^∗27:05⁺ transgenic mice and in patients undergoing HLA-mismatched hematopoietic cell transplantation (HCT), NK cells derived from human CD34⁺ stem cells were educated by HLA from both donor hematopoietic cells and host stromal cells. Furthermore, mature human KIR3DL1⁺ NK cells gained reactivity after adoptive transfer to HLA-B^∗27:05⁺ mice or bone marrow chimeric mice where HLA-B^∗27:05 was restricted to either the hematopoietic or stromal compartment. Silencing of HLA in primary NK cells diminished NK cell reactivity, while acquisition of HLA from neighboring cells increased NK cell reactivity. Altogether, these findings reveal roles for cell-extrinsic HLA in driving NK cell reactivity upward, and cell-intrinsic HLA in maintaining NK cell education.

Idioma original	English
Páginas (desde-hasta)	280-291
Número de páginas	12
Publicación	Immunity
Volumen	45
N.º	2
DOI	https://doi.org/10.1016/j.immuni.2016.07.005
Estado	Published - 2016
Publicado de forma externa	Sí

Nota bibliográfica

Funding Information:
We thank Dr. Thomas A. Waldmann (National Cancer Institute) for cDNA clones for human IL-15 and human IL-15Rα. We thank Dr. Stuart Tangye (Garvan Institute) for providing the mouse pre-B cell line Ba/F3, immortalized with mouse IL-3 gene. The authors thank Drs. Joseph Sun and Alan Hanash (MSKCC) for helpful comments on the manuscript. We are grateful to Chi-Hang Cheung, Jean-Benoît Le Luduec, Shajoti Rahman, and Mimi Tang for technical assistance. This work was supported by NIH P01 (CA23766) and NIH R01 HL088134 to K.C.H.; NIH NCI CA08747 and CA023766 to B.D.; and core grant (CA034196) and NIH R24OOD018259 and UC4DK104218 to L.D.S. and D.L.G.. Additional support was provided from the William H. Goodwin and Alice T. Goodwin and the Commonwealth Foundation for Cancer Research and the Helmsley Charitable Trust 2012PG-T1D018 (B.D.). D.L.G. receives grant support and is a consultant for The Jackson Laboratory.

Publisher Copyright:
© 2016 Elsevier Inc.

ASJC Scopus Subject Areas

Immunology and Allergy
Immunology
Infectious Diseases

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title = "Cell-Extrinsic MHC Class I Molecule Engagement Augments Human NK Cell Education Programmed by Cell-Intrinsic MHC Class I",

abstract = "The effector potential of NK cells is counterbalanced by their sensitivity to inhibition by “self” MHC class I molecules in a process called “education.” In humans, interactions between inhibitory killer immunoglobulin-like receptors (KIR) and human MHC (HLA) mediate NK cell education. In HLA-B∗27:05+ transgenic mice and in patients undergoing HLA-mismatched hematopoietic cell transplantation (HCT), NK cells derived from human CD34+ stem cells were educated by HLA from both donor hematopoietic cells and host stromal cells. Furthermore, mature human KIR3DL1+ NK cells gained reactivity after adoptive transfer to HLA-B∗27:05+ mice or bone marrow chimeric mice where HLA-B∗27:05 was restricted to either the hematopoietic or stromal compartment. Silencing of HLA in primary NK cells diminished NK cell reactivity, while acquisition of HLA from neighboring cells increased NK cell reactivity. Altogether, these findings reveal roles for cell-extrinsic HLA in driving NK cell reactivity upward, and cell-intrinsic HLA in maintaining NK cell education.",

author = "Boudreau, {Jeanette E.} and Liu, {Xiao Rong} and Zeguo Zhao and Aaron Zhang and Shultz, {Leonard D.} and Greiner, {Dale L.} and Bo Dupont and Hsu, {Katharine C.}",

note = "Funding Information: We thank Dr. Thomas A. Waldmann (National Cancer Institute) for cDNA clones for human IL-15 and human IL-15Rα. We thank Dr. Stuart Tangye (Garvan Institute) for providing the mouse pre-B cell line Ba/F3, immortalized with mouse IL-3 gene. The authors thank Drs. Joseph Sun and Alan Hanash (MSKCC) for helpful comments on the manuscript. We are grateful to Chi-Hang Cheung, Jean-Beno{\^i}t Le Luduec, Shajoti Rahman, and Mimi Tang for technical assistance. This work was supported by NIH P01 (CA23766) and NIH R01 HL088134 to K.C.H.; NIH NCI CA08747 and CA023766 to B.D.; and core grant (CA034196) and NIH R24OOD018259 and UC4DK104218 to L.D.S. and D.L.G.. Additional support was provided from the William H. Goodwin and Alice T. Goodwin and the Commonwealth Foundation for Cancer Research and the Helmsley Charitable Trust 2012PG-T1D018 (B.D.). D.L.G. receives grant support and is a consultant for The Jackson Laboratory. Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",

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AU - Liu, Xiao Rong

AU - Zhao, Zeguo

AU - Zhang, Aaron

AU - Shultz, Leonard D.

AU - Greiner, Dale L.

AU - Dupont, Bo

AU - Hsu, Katharine C.

N1 - Funding Information: We thank Dr. Thomas A. Waldmann (National Cancer Institute) for cDNA clones for human IL-15 and human IL-15Rα. We thank Dr. Stuart Tangye (Garvan Institute) for providing the mouse pre-B cell line Ba/F3, immortalized with mouse IL-3 gene. The authors thank Drs. Joseph Sun and Alan Hanash (MSKCC) for helpful comments on the manuscript. We are grateful to Chi-Hang Cheung, Jean-Benoît Le Luduec, Shajoti Rahman, and Mimi Tang for technical assistance. This work was supported by NIH P01 (CA23766) and NIH R01 HL088134 to K.C.H.; NIH NCI CA08747 and CA023766 to B.D.; and core grant (CA034196) and NIH R24OOD018259 and UC4DK104218 to L.D.S. and D.L.G.. Additional support was provided from the William H. Goodwin and Alice T. Goodwin and the Commonwealth Foundation for Cancer Research and the Helmsley Charitable Trust 2012PG-T1D018 (B.D.). D.L.G. receives grant support and is a consultant for The Jackson Laboratory. Publisher Copyright: © 2016 Elsevier Inc.

PY - 2016

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N2 - The effector potential of NK cells is counterbalanced by their sensitivity to inhibition by “self” MHC class I molecules in a process called “education.” In humans, interactions between inhibitory killer immunoglobulin-like receptors (KIR) and human MHC (HLA) mediate NK cell education. In HLA-B∗27:05+ transgenic mice and in patients undergoing HLA-mismatched hematopoietic cell transplantation (HCT), NK cells derived from human CD34+ stem cells were educated by HLA from both donor hematopoietic cells and host stromal cells. Furthermore, mature human KIR3DL1+ NK cells gained reactivity after adoptive transfer to HLA-B∗27:05+ mice or bone marrow chimeric mice where HLA-B∗27:05 was restricted to either the hematopoietic or stromal compartment. Silencing of HLA in primary NK cells diminished NK cell reactivity, while acquisition of HLA from neighboring cells increased NK cell reactivity. Altogether, these findings reveal roles for cell-extrinsic HLA in driving NK cell reactivity upward, and cell-intrinsic HLA in maintaining NK cell education.

AB - The effector potential of NK cells is counterbalanced by their sensitivity to inhibition by “self” MHC class I molecules in a process called “education.” In humans, interactions between inhibitory killer immunoglobulin-like receptors (KIR) and human MHC (HLA) mediate NK cell education. In HLA-B∗27:05+ transgenic mice and in patients undergoing HLA-mismatched hematopoietic cell transplantation (HCT), NK cells derived from human CD34+ stem cells were educated by HLA from both donor hematopoietic cells and host stromal cells. Furthermore, mature human KIR3DL1+ NK cells gained reactivity after adoptive transfer to HLA-B∗27:05+ mice or bone marrow chimeric mice where HLA-B∗27:05 was restricted to either the hematopoietic or stromal compartment. Silencing of HLA in primary NK cells diminished NK cell reactivity, while acquisition of HLA from neighboring cells increased NK cell reactivity. Altogether, these findings reveal roles for cell-extrinsic HLA in driving NK cell reactivity upward, and cell-intrinsic HLA in maintaining NK cell education.

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ER -

Cell-Extrinsic MHC Class I Molecule Engagement Augments Human NK Cell Education Programmed by Cell-Intrinsic MHC Class I

Resumen

Nota bibliográfica

ASJC Scopus Subject Areas

ODS de las Naciones Unidas

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