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CD2 Promotes Human Natural Killer Cell Membrane Nanotube Formation

Membrane nanotubes are thin membranous projections that physically connect two cells. While nanotubes have been studied in human natural killer (NK) cells and are implicated in aiding NK cell cytotoxic function, requirements for their formation to susceptible target cells remain incompletely underst...

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Detalles Bibliográficos
Autores principales: Comerci, Colin J., Mace, Emily M., Banerjee, Pinaki P., Orange, Jordan S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3480409/
https://www.ncbi.nlm.nih.gov/pubmed/23112830
http://dx.doi.org/10.1371/journal.pone.0047664
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author Comerci, Colin J.
Mace, Emily M.
Banerjee, Pinaki P.
Orange, Jordan S.
author_facet Comerci, Colin J.
Mace, Emily M.
Banerjee, Pinaki P.
Orange, Jordan S.
author_sort Comerci, Colin J.
collection PubMed
description Membrane nanotubes are thin membranous projections that physically connect two cells. While nanotubes have been studied in human natural killer (NK) cells and are implicated in aiding NK cell cytotoxic function, requirements for their formation to susceptible target cells remain incompletely understood. Here we demonstrate that the CD2-CD58/48 receptor-ligand interaction promotes and is required for nanotube formation in human NK cells. In the CD2(−) NK cell line YTS, a stable CD2 expression variant enabled effective nanotube formation, and was associated with better cytotoxic function. Importantly, only interactions between an NK cell and a susceptible target cell were associated with multiple nanotubes and the number of nanotubes was inversely correlated with their length. Quantitative live cell fluorescence microscopy of CD2 nanotubes revealed time-dependent enrichment and localization of CD2 to the nanotube tip, and blocking CD2 receptor-ligand interactions prevented nanotube formation. Increased nanotube formation was not simply a feature of receptor-ligand pairing, as a KIR-MHC interaction in the same cell line system failed to promote nanotube formation. Additionally, blocking LFA-1-ICAM and 2B4-CD48 receptor-ligand interactions failed to inhibit nanotube formation. Thus only specific receptor-ligand pairs promote nanotubes. CD2 also promoted nanotube formation in ex vivo NK cells suggesting that CD2 plays a crucial role in the generation of nanotubes between an NK cell and its target.
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spelling pubmed-34804092012-10-30 CD2 Promotes Human Natural Killer Cell Membrane Nanotube Formation Comerci, Colin J. Mace, Emily M. Banerjee, Pinaki P. Orange, Jordan S. PLoS One Research Article Membrane nanotubes are thin membranous projections that physically connect two cells. While nanotubes have been studied in human natural killer (NK) cells and are implicated in aiding NK cell cytotoxic function, requirements for their formation to susceptible target cells remain incompletely understood. Here we demonstrate that the CD2-CD58/48 receptor-ligand interaction promotes and is required for nanotube formation in human NK cells. In the CD2(−) NK cell line YTS, a stable CD2 expression variant enabled effective nanotube formation, and was associated with better cytotoxic function. Importantly, only interactions between an NK cell and a susceptible target cell were associated with multiple nanotubes and the number of nanotubes was inversely correlated with their length. Quantitative live cell fluorescence microscopy of CD2 nanotubes revealed time-dependent enrichment and localization of CD2 to the nanotube tip, and blocking CD2 receptor-ligand interactions prevented nanotube formation. Increased nanotube formation was not simply a feature of receptor-ligand pairing, as a KIR-MHC interaction in the same cell line system failed to promote nanotube formation. Additionally, blocking LFA-1-ICAM and 2B4-CD48 receptor-ligand interactions failed to inhibit nanotube formation. Thus only specific receptor-ligand pairs promote nanotubes. CD2 also promoted nanotube formation in ex vivo NK cells suggesting that CD2 plays a crucial role in the generation of nanotubes between an NK cell and its target. Public Library of Science 2012-10-24 /pmc/articles/PMC3480409/ /pubmed/23112830 http://dx.doi.org/10.1371/journal.pone.0047664 Text en © 2012 Comerci et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Comerci, Colin J.
Mace, Emily M.
Banerjee, Pinaki P.
Orange, Jordan S.
CD2 Promotes Human Natural Killer Cell Membrane Nanotube Formation
title CD2 Promotes Human Natural Killer Cell Membrane Nanotube Formation
title_full CD2 Promotes Human Natural Killer Cell Membrane Nanotube Formation
title_fullStr CD2 Promotes Human Natural Killer Cell Membrane Nanotube Formation
title_full_unstemmed CD2 Promotes Human Natural Killer Cell Membrane Nanotube Formation
title_short CD2 Promotes Human Natural Killer Cell Membrane Nanotube Formation
title_sort cd2 promotes human natural killer cell membrane nanotube formation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3480409/
https://www.ncbi.nlm.nih.gov/pubmed/23112830
http://dx.doi.org/10.1371/journal.pone.0047664
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