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Intra- and Extracellular Effector Vesicles From Human T And NK Cells: Same-Same, but Different?
Cytotoxic T lymphocytes (CTL) and Natural Killer (NK) cells utilize an overlapping effector arsenal for the elimination of target cells. It was initially proposed that all cytotoxic effector proteins are stored in lysosome-related effector vesicles (LREV) termed “secretory lysosomes” as a common sto...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8733945/ https://www.ncbi.nlm.nih.gov/pubmed/35003134 http://dx.doi.org/10.3389/fimmu.2021.804895 |
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author | Lettau, Marcus Janssen, Ottmar |
author_facet | Lettau, Marcus Janssen, Ottmar |
author_sort | Lettau, Marcus |
collection | PubMed |
description | Cytotoxic T lymphocytes (CTL) and Natural Killer (NK) cells utilize an overlapping effector arsenal for the elimination of target cells. It was initially proposed that all cytotoxic effector proteins are stored in lysosome-related effector vesicles (LREV) termed “secretory lysosomes” as a common storage compartment and are only released into the immunological synapse formed between the effector and target cell. The analysis of enriched LREV, however, revealed an uneven distribution of individual effectors in morphologically distinct vesicular entities. Two major populations of LREV were distinguished based on their protein content and signal requirements for degranulation. Light vesicles carrying FasL and 15 kDa granulysin are released in a PKC-dependent and Ca(2+)-independent manner, whereas dense granules containing perforin, granzymes and 9 kDa granulysin require Ca(2+)-signaling as a hallmark of classical degranulation. Notably, both types of LREV do not only contain the mentioned cytolytic effectors, but also store and transport diverse other immunomodulatory proteins including MHC class I and II, costimulatory and adhesion molecules, enzymes (i.e. CD26/DPP4) or cytokines. Interestingly, the recent analyses of CTL- or NK cell-derived extracellular vesicles (EV) revealed the presence of a related mixture of proteins in microvesicles or exosomes that in fact resemble fingerprints of the cells of origin. This overlapping protein profile indicates a direct relation of intra- and extracellular vesicles. Since EV potentially also interact with cells at distant sites (apart from the IS), they might act as additional effector vesicles or intercellular communicators in a more systemic fashion. |
format | Online Article Text |
id | pubmed-8733945 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-87339452022-01-07 Intra- and Extracellular Effector Vesicles From Human T And NK Cells: Same-Same, but Different? Lettau, Marcus Janssen, Ottmar Front Immunol Immunology Cytotoxic T lymphocytes (CTL) and Natural Killer (NK) cells utilize an overlapping effector arsenal for the elimination of target cells. It was initially proposed that all cytotoxic effector proteins are stored in lysosome-related effector vesicles (LREV) termed “secretory lysosomes” as a common storage compartment and are only released into the immunological synapse formed between the effector and target cell. The analysis of enriched LREV, however, revealed an uneven distribution of individual effectors in morphologically distinct vesicular entities. Two major populations of LREV were distinguished based on their protein content and signal requirements for degranulation. Light vesicles carrying FasL and 15 kDa granulysin are released in a PKC-dependent and Ca(2+)-independent manner, whereas dense granules containing perforin, granzymes and 9 kDa granulysin require Ca(2+)-signaling as a hallmark of classical degranulation. Notably, both types of LREV do not only contain the mentioned cytolytic effectors, but also store and transport diverse other immunomodulatory proteins including MHC class I and II, costimulatory and adhesion molecules, enzymes (i.e. CD26/DPP4) or cytokines. Interestingly, the recent analyses of CTL- or NK cell-derived extracellular vesicles (EV) revealed the presence of a related mixture of proteins in microvesicles or exosomes that in fact resemble fingerprints of the cells of origin. This overlapping protein profile indicates a direct relation of intra- and extracellular vesicles. Since EV potentially also interact with cells at distant sites (apart from the IS), they might act as additional effector vesicles or intercellular communicators in a more systemic fashion. Frontiers Media S.A. 2021-12-23 /pmc/articles/PMC8733945/ /pubmed/35003134 http://dx.doi.org/10.3389/fimmu.2021.804895 Text en Copyright © 2021 Lettau and Janssen https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Lettau, Marcus Janssen, Ottmar Intra- and Extracellular Effector Vesicles From Human T And NK Cells: Same-Same, but Different? |
title | Intra- and Extracellular Effector Vesicles From Human T And NK Cells: Same-Same, but Different? |
title_full | Intra- and Extracellular Effector Vesicles From Human T And NK Cells: Same-Same, but Different? |
title_fullStr | Intra- and Extracellular Effector Vesicles From Human T And NK Cells: Same-Same, but Different? |
title_full_unstemmed | Intra- and Extracellular Effector Vesicles From Human T And NK Cells: Same-Same, but Different? |
title_short | Intra- and Extracellular Effector Vesicles From Human T And NK Cells: Same-Same, but Different? |
title_sort | intra- and extracellular effector vesicles from human t and nk cells: same-same, but different? |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8733945/ https://www.ncbi.nlm.nih.gov/pubmed/35003134 http://dx.doi.org/10.3389/fimmu.2021.804895 |
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