Abstract
Bovine leukemia virus (BLV) is a retrovirus that is highly prevalent in US dairy herds: over 83% are BLV infected and the within-herd infection rate can be almost 50% on average. While BLV is known to cause lymphosarcomas, only 5% or fewer infected cattle will develop lymphoma; this low prevalence of cancer has historically not been a concern to dairy producers. However, more recent research has found that BLV+ cows without lymphoma produce less milk and have shorter lifespans than uninfected herdmates. It has been hypothesized that BLV infection interferes with normal immune function in infected cattle, and this could lead to reduced dairy production. To assess how naturally infected BLV+ cows responded to a primary and secondary immune challenge, 10 BLV+ and 10 BLV− cows were injected subcutaneously with keyhole limpet hemocyanin (KLH) and dimethyldioctadecylammonium bromide. B- and T-cell responses were characterized over the following 28 days. A total of 56 days after primary KLH exposure, cows were re-injected with KLH and B- and T-cell responses were characterized again over the following 28 days. BLV+ cows produced less KLH-specific IgM after primary immune stimulation; demonstrated fewer CD45R0+ B cells, altered proportions of CD5+ B cells, altered expression of CD5 on CD5+ B cells, and reduced MHCII surface expression on B cells ex vivo; exhibited reduced B-cell activation in vitro; and displayed an increase in BLV proviral load after KLH exposure. In addition, BLV+ cows had a reduced CD45R0+γδ+ T-cell population in the periphery and demonstrated a greater prevalence of IL4-producing T cells in vitro. All together, our results demonstrate that both B- and T-cell immunities are disrupted in BLV+ cows and that antigen-specific deficiencies can be detected in BLV+ cows even after a primary immune exposure.
Highlights
In contrast to IgM production, Bovine leukemia virus (BLV)+ and BLV− cows produced equivalent levels of IgG1 (p = 0.6715) (Figure 1B) and IgG2 (p = 0.9437) (Figure 1C) after both primary and secondary keyhole limpet hemocyanin (KLH) inoculations. These data support recent evidence that BLV infection interferes with IgM antibody production after both a primary immune challenge and a common vaccine booster injection [10]
We investigated how BLV+ dairy cows respond to both a primary immune stimulation and a secondary immune stimulation
After exposing BLV+ and BLV− cows to a noninfectious antigen (KLH), both B- and T-cell responses were tracked over a 3-month period to measure both the primary and secondary immune responses
Summary
Bovine leukemia virus (BLV) is a δ-retrovirus [1] that infects over 83% of dairy herds in the United States; as many as 40% of all US dairy cattle are infected [2]. BLV is the causative agent of enzootic bovine leukosis (EBL), where BLV+ cattle develop malignant lymphoma or leukemia [3]. Bovine leukemia virus infection reduces both milk production [2] and longevity [4] in infected dairy cows. While it is unclear how BLV interferes with milk production and lifespan, one hypothesis is that BLV causes immune dysregulation, which could put BLV+ cattle at an increased risk for other infections. When investigating immunity in naturally infected BLV+ cattle, many studies were unable to control for how much antigen exposure occurred before or after BLV infection
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