While T cell activity has not

While γδ T cell activity has not been well characterized in the context of BLV infection, bovine γδ T cell activity in the context of many other infections has been investigated. Cattle are considered to have a high proportion of γδ T faah inhibitors in the periphery, which is suggestive that they are of particular importance to cattle immunity (Baldwin and Telfer, 2015). Indeed, evidence suggests that γδ T cells in cattle can form memory populations in response to vaccination (Blumerman et al., 2007). In addition, WC1+ γδ T cells in cattle can produce IFNγ in response to stimulation, and this may skew immune polarization to a Th1 phenotype (Baldwin and Telfer, 2015). However, at this point it is unclear why γδ T cells from BLV+ cows have increased reactivity to stimulation in vitro, although it is possible that BLV+ cows have a higher ratio of WC1+: WC1- γδ T cells, which could explain the higher proportion of IFNγ-producing γδ T cells observed. It is also important to note that short term in vitro PBMC culture conditions can induce BLV protein expression (Frie and Coussens, 2015), so it is possible that increased reactivity of γδ T cells isolated from BLV+ cows is the result of γδ T cells that are reactive against BLV antigens, not the selected culture stimulant. However, under these culture conditions we were unable to detect BLV gp51 protein expression.
In this study, vaccination was used to determine if BLV+ cows mount a weaker immune response to stimulation. BLV+ cows tended to produce lower antigen-specific IgM and IgG2 antibody titers and displayed atypical B and T cell responses to in vitro stimulation after boost vaccination. These data support the hypothesis that BLV+ cows develop abnormal immune responses to stimulation and likely have compromised protection against other infectious diseases. The plasma antibody titers in conjunction with in vitro B and T cell activation data also warrant further investigation to understand the mechanism by which BLV infection interferes with antibody production. Further understanding of BLV’s effect on the bovine immune system is critical to ensure that the US dairy industry is equipped to assess and address the threat of BLV infection to dairy herds nationwide.

Acknowledgements
The authors gratefully acknowledge the contributions of other members of the Molecular Pathogenesis Laboratory: Dr. Jonathon Roussey, Jenna Carter, Hannah Dewald, Rachel Courville, Kristina Meier and Thilo Hamlischer. The authors also would like to thank the manager of the Michigan State University Dairy Teaching and Research Center, Robert West, as well as Kerry Nobis and the Nobis Dairy Farms. This work was supported by the United States Department of Agriculture and the National Institute of Food and Agriculture (2014-67015-21632, 2014-68004-21881, and 2016-67011-24713), Michigan AgBioResearch, the Michigan Alliance for Animal Agriculture and the Michigan Milk Producers Association.

Introduction
In swine production, weaning is a stressful period that reduces growth performance (Pluske et al., 1997), induces major perturbation of the intestinal microbiota (Castillo et al., 2007), and impairs intestinal barrier and immune functions and increases susceptibility to pathogenic bacteria such as enterotoxigenic Escherichia coli (Schroyen et al., 2013). Moreover, selection for improved sow prolificacy has resulted in a greater number of newborn piglets per litter and an increased proportion of low-birth-weight (LW) piglets within litters (Milligan et al., 2002; Quesnel et al., 2008). Therefore, such heterogeneity of birth weight induced by hyperprolificity generates distinct populations of piglets of low weight (LW) and high weight (HW) within litters and is likely to affect the access of piglets to colostrum and milk during the lactation, with consequences for future growth performance and resistance to diseases (Douglas et al., 2014). Indeed, the growth performance of LW piglets during lactation and after weaning is impaired in comparison with that of heavier piglets (Quiniou et al., 2002; Berard et al., 2008; Beaulieu et al., 2010). There is also evidence that piglet weight at birth and environmental conditions influence immune competence development (Schokker et al., 2014; Hu et al., 2015).