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

Sci Rep. 2021 Jul 22;11(1):14965. doi: 10.1038/s41598-021-94017-7.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / blood
  • Exome Sequencing
  • 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*

Substances

  • Antibodies, Neutralizing
  • Receptors, Antigen, T-Cell, gamma-delta