Generation and first characterization of TRDC-knockout pigs lacking γδ T cells.
Animals
Antibodies, Neutralizing
/ blood
Gene Expression Profiling
Gene Knockout Techniques
/ methods
Gene Regulatory Networks
Leukocytes, Mononuclear
/ immunology
Mice
Nuclear Transfer Techniques
Receptors, Antigen, T-Cell, gamma-delta
/ deficiency
Spleen
/ immunology
Swine
T-Lymphocytes
/ immunology
Exome Sequencing
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
22 07 2021
22 07 2021
Historique:
received:
23
04
2021
accepted:
29
06
2021
entrez:
23
7
2021
pubmed:
24
7
2021
medline:
10
11
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34294758
doi: 10.1038/s41598-021-94017-7
pii: 10.1038/s41598-021-94017-7
pmc: PMC8298467
doi:
Substances chimiques
Antibodies, Neutralizing
0
Receptors, Antigen, T-Cell, gamma-delta
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
14965Informations de copyright
© 2021. The Author(s).
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