Cell-Extrinsic MHC Class I Molecule Engagement Augments Human NK Cell Education Programmed by Cell-Intrinsic MHC Class I.
Immunity
; 45(2): 280-91, 2016 08 16.
Article
em En
| MEDLINE
| ID: mdl-27496730
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(∗)2705(+) 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(∗)2705(+) mice or bone marrow chimeric mice where HLA-B(∗)2705 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Autoantígenos
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Células Matadoras Naturais
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Antígeno HLA-B27
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Células Estromais
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Neoplasias Hematológicas
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Transplante de Células-Tronco de Sangue do Cordão Umbilical
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Receptores KIR3DL1
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article