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.
Highlights
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
The genomic DNA of the piglets originating from intracytoplasmic microinjection of the pX330-TRDCEX4 #1 and #2 plasmids was employed for polymerase chain reaction (PCR) (Fig. 1) and subsequent sequencing (Fig. 2) to detect genetic modifications at the TRDC gene
While healthy offspring could be obtained after embryo transfer of microinjected zygotes, somatic cell nuclear transfer (SCNT) resulted in 47.1% stillborn piglets
Summary
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. The increase in γδ T cells following vaccinia virus infection, high vaccinia virus replication in γδ T cell knockout mice, and the selective lysis of γδ T cells against vaccinia virus infected target cells indicate some role for γδ T cells during virus infections[9,10,11] To understand what they do and what role they play in different challenging situations of the immune system, a knockout animal model would be indispensable. Based on the remarkable lack of conservation between γδ T cells of different species, additional animal models are needed to understand the function of γδ T cells and to establish a unifying concept for their role during immune responses. The availability of a γδ T cells deficient animal model from a γδ T cell-high species may add important new insights in the role of this mysterious part of the adaptive immune system
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
