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bioRxiv · 10.1101/2021.03.27.437312

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

Petersen, B.·Kammerer, R.·Frenzel, A.·Hassel, P.·Dau, T. H.·Becker, R.·Breithaupt, A.·Ulrich, R.·Lucas-Hahn, A.·Meyers, G.
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Abstract

The TRDC-Locus encodes the T cell receptor delta constant region, one component of the {gamma}{delta} T cell receptor which is essential for development of {gamma}{delta} T cells. In contrast to peptide recognition by {beta} T cells, antigens activating {gamma}{delta} T cells are mostly MHC independent and not well characterized. Therefore, the function of {gamma}{delta} T cells and their contribution to protection against infections is still unclear. Higher numbers of circulating {gamma}{delta} T cells compared to mice, render the pig a suitable animal model to study {gamma}{delta} T cells. Knocking-out the porcine TRDC-locus by intracytoplasmic microinjection and somatic cell nuclear transfer resulted in healthy living {gamma}{delta} T cell deficient offspring. Flow cytometric analysis revealed that TRDC-KO pigs lack {gamma}{delta} 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 {gamma}{delta} T cells. Genome-wide transcriptome analyses in PBMC revealed a pattern of changes reflecting the impairment of known or expected {gamma}{delta} 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.

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Petersen, B., Kammerer, R., Frenzel, A., Hassel, P., Dau, T. H., Becker, R., Breithaupt, A., Ulrich, R., Lucas-Hahn, A., Meyers, G.. 2021-03-29. Generation and first characterization of TRDC-Knockout pigs lacking γδ T cells. https://doi.org/10.1101/2021.03.27.437312

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