Recent advances in γδ T cell biology: New ligands, new functions, and new translational perspectives

Gamma/delta (γδ) T-cells are a small subset of T-lymphocytes in the peripheral circulation but constitute a major T-cell population at other anatomical localizations such as the epithelial tissues. In contrast to conventional a/ß T-cells, the available number of germline genes coding for T-cell rece...

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Main Authors: Dieter Kabelitz, Julie Dechanet-Merville
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語言:英语
出版: Frontiers Media SA 2021
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author Dieter Kabelitz
Julie Dechanet-Merville
author_browse Dieter Kabelitz
Julie Dechanet-Merville
author_facet Dieter Kabelitz
Julie Dechanet-Merville
author_sort Dieter Kabelitz
collection Directory of Open Access Books
description Gamma/delta (γδ) T-cells are a small subset of T-lymphocytes in the peripheral circulation but constitute a major T-cell population at other anatomical localizations such as the epithelial tissues. In contrast to conventional a/ß T-cells, the available number of germline genes coding for T-cell receptor (TCR) variable elements of γδ T-cells is very small. Moreover, there is a prefential localization of γδ T-cells expressing given Vgamma and Vdelta genes in certain tissues. In humans, γδ T-cells expressing the Vg9Vd2-encoded TCR account for anywhere between 50 and >95% of peripheral blood γδ T-cells, whereas cells expressing non-Vd2 genes dominate in mucosal tissues. In mice, there is an ordered appearance of γδ T-cell „waves“ during embryonic development, resulting in preferential localization of γδ T-cells expressing distinct VgammaVdelta genes in the skin, the reproductive organs, or gut epithelia. The major function of γδ T-cells resides in local immunosurveillance and immune defense against infection and malignancy. This is supported by the identification of ligands that are selectively recognized by the γδ TCR. As an example, human Vgamma9Vdelta2 T-cells recognize phosphorylated metabolites („phosphoantigens“) that are secreted by many pathogens but can also be overproduced by tumor cells, providing a basis for a role of these γδ T-cells in both anti-infective and anti-tumor immunity. Similarly, the recognition of endothelial protein C receptor by human non-Vdelta2 γδ T-cells has recently been identified to provide a link for the role for such γδ T-cells in immunity against epithelial tumor cells and cytomegalovirus-infected endothelial cells. In addition to „classical“ functions such as cytokine production and cytotoxicity, recent studies suggest that subsets of γδ T-cells can exert additional functions such as regulatory activity and – quite surpisingly – „professional“ antigen-presenting capacity. It is currently not well known how this tremendous extent of functional plasticity is regulated and what is the extent of γδ TCR ligand diversity. Due to their non-MHC-restricted recognition of unusual stress-associated ligands, γδ T-cells have raised great interest as to their potential translational application in cell-based immunotherapy. Topics of this Research Focus include: Molecular insights into the activation and differentiation requirements of γδ T-cells, role of pyrophosphates and butyrophilin molecules for the activation of human γδ T-cells, role of γδ T-cells in tumor immunity and in other infectious and non-infectious diseases, and many others. We are most grateful to all colleagues who agreed to write a manuscript. Thanks to their contributions, this E-book presents an up-to-date overview on many facets of the still exciting γδ T-cells.
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spelling doab-20.500.12854ir-577582024-03-30T23:21:43Z Recent advances in γδ T cell biology: New ligands, new functions, and new translational perspectives Dieter Kabelitz Julie Dechanet-Merville R5-920 RC581-607 Infection Butyrophilin 3A1 Tumor-infiltrating lymphocytes cancer immunotherapy IL-17 Pyrophosphates thema EDItEUR::M Medicine and Nursing Gamma/delta (γδ) T-cells are a small subset of T-lymphocytes in the peripheral circulation but constitute a major T-cell population at other anatomical localizations such as the epithelial tissues. In contrast to conventional a/ß T-cells, the available number of germline genes coding for T-cell receptor (TCR) variable elements of γδ T-cells is very small. Moreover, there is a prefential localization of γδ T-cells expressing given Vgamma and Vdelta genes in certain tissues. In humans, γδ T-cells expressing the Vg9Vd2-encoded TCR account for anywhere between 50 and >95% of peripheral blood γδ T-cells, whereas cells expressing non-Vd2 genes dominate in mucosal tissues. In mice, there is an ordered appearance of γδ T-cell „waves“ during embryonic development, resulting in preferential localization of γδ T-cells expressing distinct VgammaVdelta genes in the skin, the reproductive organs, or gut epithelia. The major function of γδ T-cells resides in local immunosurveillance and immune defense against infection and malignancy. This is supported by the identification of ligands that are selectively recognized by the γδ TCR. As an example, human Vgamma9Vdelta2 T-cells recognize phosphorylated metabolites („phosphoantigens“) that are secreted by many pathogens but can also be overproduced by tumor cells, providing a basis for a role of these γδ T-cells in both anti-infective and anti-tumor immunity. Similarly, the recognition of endothelial protein C receptor by human non-Vdelta2 γδ T-cells has recently been identified to provide a link for the role for such γδ T-cells in immunity against epithelial tumor cells and cytomegalovirus-infected endothelial cells. In addition to „classical“ functions such as cytokine production and cytotoxicity, recent studies suggest that subsets of γδ T-cells can exert additional functions such as regulatory activity and – quite surpisingly – „professional“ antigen-presenting capacity. It is currently not well known how this tremendous extent of functional plasticity is regulated and what is the extent of γδ TCR ligand diversity. Due to their non-MHC-restricted recognition of unusual stress-associated ligands, γδ T-cells have raised great interest as to their potential translational application in cell-based immunotherapy. Topics of this Research Focus include: Molecular insights into the activation and differentiation requirements of γδ T-cells, role of pyrophosphates and butyrophilin molecules for the activation of human γδ T-cells, role of γδ T-cells in tumor immunity and in other infectious and non-infectious diseases, and many others. We are most grateful to all colleagues who agreed to write a manuscript. Thanks to their contributions, this E-book presents an up-to-date overview on many facets of the still exciting γδ T-cells. 2021-02-12T01:05:35Z 2021-02-12T01:05:35Z 2016-04-07 11:22:02 2016 book 18900 16648714 9782889197842 https://directory.doabooks.org/handle/20.500.12854/57758 eng Frontiers Research Topics image/jpeg Attribution 4.0 International http://www.frontiersin.org/books/Recent_Advances_in_d_T-Cell_Biology_New_Ligands_New_Functions_and_New_Translational_Perspectives/801 http://journal.frontiersin.org/researchtopic/2041/recent-advances-in-t-cell-biology-new-ligands-new-functions-translational-perspective Frontiers Media SA 10.3389/978-2-88919-784-2 10.3389/978-2-88919-784-2 bf5ce210-e72e-4860-ba9b-c305640ff3ae 9782889197842 269 open access
spellingShingle R5-920
RC581-607
Infection
Butyrophilin 3A1
Tumor-infiltrating lymphocytes
cancer immunotherapy
IL-17
Pyrophosphates
thema EDItEUR::M Medicine and Nursing
Dieter Kabelitz
Julie Dechanet-Merville
Recent advances in γδ T cell biology: New ligands, new functions, and new translational perspectives
title Recent advances in γδ T cell biology: New ligands, new functions, and new translational perspectives
title_full Recent advances in γδ T cell biology: New ligands, new functions, and new translational perspectives
title_fullStr Recent advances in γδ T cell biology: New ligands, new functions, and new translational perspectives
title_full_unstemmed Recent advances in γδ T cell biology: New ligands, new functions, and new translational perspectives
title_short Recent advances in γδ T cell biology: New ligands, new functions, and new translational perspectives
title_sort recent advances in γδ t cell biology new ligands new functions and new translational perspectives
topic R5-920
RC581-607
Infection
Butyrophilin 3A1
Tumor-infiltrating lymphocytes
cancer immunotherapy
IL-17
Pyrophosphates
thema EDItEUR::M Medicine and Nursing
topic_facet R5-920
RC581-607
Infection
Butyrophilin 3A1
Tumor-infiltrating lymphocytes
cancer immunotherapy
IL-17
Pyrophosphates
thema EDItEUR::M Medicine and Nursing
url 18900
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