Generation and first characterization of TRDC-knockout pigs lacking γδ T cells

Abstract The TRDC-locus encodes the T cell receptor delta constant region, one component of the γδ T cell receptor which is essential for development of γδ T cells. In contrast to peptide recognition by αβ T cells, antigens activating γδ T cells are mostly MHC independent and not well characterized....

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Autores principales:	Bjoern Petersen, Robert Kammerer, Antje Frenzel, Petra Hassel, Tung Huy Dau, Roswitha Becker, Angele Breithaupt, Reiner Georg Ulrich, Andrea Lucas-Hahn, Gregor Meyers
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9fee6125b0b4471aa566d3bbc4915e51
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spelling	oai:doaj.org-article:9fee6125b0b4471aa566d3bbc4915e512021-12-02T17:57:16ZGeneration and first characterization of TRDC-knockout pigs lacking γδ T cells10.1038/s41598-021-94017-72045-2322https://doaj.org/article/9fee6125b0b4471aa566d3bbc4915e512021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94017-7https://doaj.org/toc/2045-2322Abstract The TRDC-locus encodes the T cell receptor delta constant region, one component of the γδ T cell receptor which is essential for development of γδ T cells. In contrast to peptide recognition by αβ T cells, antigens activating γδ T cells are mostly MHC independent and not well characterized. Therefore, the function of γδ T cells and their contribution to protection against infections is still unclear. Higher numbers of circulating γδ T cells compared to mice, render the pig a suitable animal model to study γδ T cells. Knocking-out the porcine TRDC-locus by intracytoplasmic microinjection and somatic cell nuclear transfer resulted in healthy living γδ T cell deficient offspring. Flow cytometric analysis revealed that TRDC-KO pigs lack γδ T cells in peripheral blood mononuclear cells (PBMC) and spleen cells. The composition of the remaining leucocyte subpopulations was not affected by the depletion of γδ T cells. Genome-wide transcriptome analyses in PBMC revealed a pattern of changes reflecting the impairment of known or expected γδ T cell dependent pathways. Histopathology did not reveal developmental abnormalities of secondary lymphoid tissues. However, in a vaccination experiment the KO pigs stayed healthy but had a significantly lower neutralizing antibody titer as the syngenic controls.Bjoern PetersenRobert KammererAntje FrenzelPetra HasselTung Huy DauRoswitha BeckerAngele BreithauptReiner Georg UlrichAndrea Lucas-HahnGregor MeyersNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Bjoern Petersen Robert Kammerer Antje Frenzel Petra Hassel Tung Huy Dau Roswitha Becker Angele Breithaupt Reiner Georg Ulrich Andrea Lucas-Hahn Gregor Meyers Generation and first characterization of TRDC-knockout pigs lacking γδ T cells
description	Abstract The TRDC-locus encodes the T cell receptor delta constant region, one component of the γδ T cell receptor which is essential for development of γδ T cells. In contrast to peptide recognition by αβ T cells, antigens activating γδ T cells are mostly MHC independent and not well characterized. Therefore, the function of γδ T cells and their contribution to protection against infections is still unclear. Higher numbers of circulating γδ T cells compared to mice, render the pig a suitable animal model to study γδ T cells. Knocking-out the porcine TRDC-locus by intracytoplasmic microinjection and somatic cell nuclear transfer resulted in healthy living γδ T cell deficient offspring. Flow cytometric analysis revealed that TRDC-KO pigs lack γδ T cells in peripheral blood mononuclear cells (PBMC) and spleen cells. The composition of the remaining leucocyte subpopulations was not affected by the depletion of γδ T cells. Genome-wide transcriptome analyses in PBMC revealed a pattern of changes reflecting the impairment of known or expected γδ T cell dependent pathways. Histopathology did not reveal developmental abnormalities of secondary lymphoid tissues. However, in a vaccination experiment the KO pigs stayed healthy but had a significantly lower neutralizing antibody titer as the syngenic controls.
format	article
author	Bjoern Petersen Robert Kammerer Antje Frenzel Petra Hassel Tung Huy Dau Roswitha Becker Angele Breithaupt Reiner Georg Ulrich Andrea Lucas-Hahn Gregor Meyers
author_facet	Bjoern Petersen Robert Kammerer Antje Frenzel Petra Hassel Tung Huy Dau Roswitha Becker Angele Breithaupt Reiner Georg Ulrich Andrea Lucas-Hahn Gregor Meyers
author_sort	Bjoern Petersen
title	Generation and first characterization of TRDC-knockout pigs lacking γδ T cells
title_short	Generation and first characterization of TRDC-knockout pigs lacking γδ T cells
title_full	Generation and first characterization of TRDC-knockout pigs lacking γδ T cells
title_fullStr	Generation and first characterization of TRDC-knockout pigs lacking γδ T cells
title_full_unstemmed	Generation and first characterization of TRDC-knockout pigs lacking γδ T cells
title_sort	generation and first characterization of trdc-knockout pigs lacking γδ t cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/9fee6125b0b4471aa566d3bbc4915e51
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Generation and first characterization of TRDC-knockout pigs lacking γδ T cells

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