Rapid and Transient Activation of γδ T Cells to IFN-γ Production, NK Cell-Like Killing, and Antigen Processing during Acute Virus Infection

Abstract

γδ T cells are the majority peripheral blood T cells in young cattle. The role of γδ T cells in innate responses against infection with foot-and-mouth disease virus was analyzed on consecutive 5 d following infection. Before infection, bovine WC1+ γδ T cells expressed a nonactivated phenotype relative to CD62L, CD45RO, and CD25 expression and did not produce IFN-γ ex vivo. Additionally, CD335 expression was lacking and no spontaneous target cell lysis could be detected in vitro, although perforin was detectable at a very low level. MHC class II and CD13 expression were also lacking. Following infection with foot-and-mouth disease virus, expression of CD62L and CD45RO was greatly reduced on WC1+ γδ T cells, and unexpectedly, CD45RO expression did not recover. A transient increase in expression of CD25 correlated with production of IFN-γ. Expression of CD335 and production of perforin were detected on a subset of γδ T cells, and this correlated with an increased spontaneous killing of xenogeneic target cells. Furthermore, increased MHC class II expression was detected on WC1+ γδ T cells, and these cells processed protein Ags. These activities are rapidly induced, within 3 d, and wane by 5 d following infection. All of these functions, NK-like killing, Ag processing, and IFN-γ production, have been demonstrated for these cells in various species. However, these results are unique in that all these functions are detected in the same samples of WC1+ γδ T cells, suggesting a pivotal role of these cells in controlling virus infection.

The presence of CD25 on bovine WC1+ γδ T cells is positively correlated with their production of IL-10 and TGF-β, but not IFN-γ

“…CD25 expression substantially increased on both WC1.1 + and WC1.2 + cells after only 1 day of culture with Con A relative to that on cells cultured with medium. Furthermore, the diagrams presented in Toka et al (2011) show that about 20% of WC1 + lymphocytes collected from healthy 3-5-month-old calves constitutively expressed CD25, whereas the value was several times higher 2-3 days after infection of the animals with the O1 Manisa strain of FMDV. The study conducted by Sanbulte and Roth (2002) + cells in the same manner, the percentage of cells which produce only IFN-γ, only IL-10 or which co-produce IFN-γ and IL-10 is 32.83%, 52.81% and 14.36%, respectively.…”

“…The WC1.1 + cells appeared to be the main producers of IFN-γ, whereas the WC1.2 + cells have been reported to proliferate in response to stimulation with mitogens (Rogers et al 2005a, b). Although the two populations can be distinguished, there is too little information to conclude that they differ functionally (Toka et al 2011). Several investigations have been designed specifically to determine the function of bovine γδ T cells, and particularly cells expressing WC1, in immune responses against various pathogens.…”

Toll-like receptors, IFN-γ and IL-12 expression in bovine leukemia virus-infected animals with low or high proviral load

“…γδ + T cells are found in large proportions in cattle; they may comprise up to 60% of circulating lymphocytes in calves and decrease in adults up to 8-18% (Baldwin and Telfer, 2015). They can recognize antigens in their native form without MHC class I or II presentation (Baldwin and Telfer, 2015) and they have been shown to mount cytotoxic, cytokines and proliferative responses in several viral infections in cattle (Amadori et al, 1995;Bukowski et al, 1994;Silflow et al, 2005;Toka et al, 2011). γδ + T lymphocytes play a crucial role against intracellular pathogens, linking innate and specific immune responses (Baldwin and Telfer, 2015;Pollock and Welsh, 2002), and even a subpopulation of them can act as immune regulatory cells (Hoek et al, 2009).…”

Comparative Studies on the Distribution and Population of Immunocompetent Cells in Bovine Hemal Node, Lymph Node and Spleen

“…In addition, young cattle have high levels of γδ T cells, which are found in blood circulation and can respond to autologous molecules and recognize non-peptide antigens [18,23,25,30,31]. It has also been reported that γδ T cells can act as antigen-presenting cells; but, the induction sites for profes- sional antigen-presenting γδ T cells have not been fully determined in vivo [6,12,31,39]. We speculate that γδ T cells, which are distributed in the lymphatic cord along the sinus of HN, have a potential for antigen presenting cell (manuscript in preparation).…”