Dairy Cows Naturally Infected with Bovine Leukemia Virus Exhibit Abnormal B- and T-Cell Phenotypes after Primary and Secondary Exposures to Keyhole Limpet Hemocyanin
Dairy Cows Naturally Infected with Bovine Leukemia Virus Exhibit Abnormal B- and T-Cell Phenotypes after Primary and Secondary Exposures to Keyhole Limpet Hemocyanin
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DOI：
10.3389/fvets.2017.00112
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发表时间：
2017-07-14
影响因子：
3.2
通讯作者：
Coussens, Paul M.
中科院分区：
文献类型：
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作者：
Frie, Meredith C.;Sporer, Kelly R. B.;Coussens, Paul M.
牛白血病病毒（BLV）是一种在美国奶牛群中高度流行的逆转录病毒：超过 83% 的奶牛感染 BLV，牛群内平均感染率接近 50%。虽然已知 BLV 会引起淋巴肉瘤，但只有 5% 或更少的受感染牛会患上淋巴瘤；乳制品生产商历来并不担心癌症患病率如此之低。然而，最近的研究发现，与未感染的牧群相比，未患淋巴瘤的 BLV+ 奶牛产奶量较少，寿命也较短。据推测，BLV 感染会干扰受感染牛的正常免疫功能，这可能导致乳制品产量减少。为了评估自然感染的 BLV+ 奶牛对初次和二次免疫挑战的反应，对 10 头 BLV+ 和 10 头 BLV- 奶牛皮下注射匙孔血蓝蛋白 (KLH) 和二甲基双十八烷基溴化铵。在接下来的 28 天内对 B 细胞和 T 细胞反应进行了表征。初次接触 KLH 后总共 56 天，奶牛重新注射 KLH，并在接下来的 28 天再次表征 B 和 T 细胞反应。 BLV+ 奶牛在初次免疫刺激后产生较少的 KLH 特异性 IgM；证明 CD45R0(+) B 细胞减少、CD5(+) B 细胞比例改变、CD5(+) B 细胞上 CD5 表达改变以及离体 B 细胞上 MHCII 表面表达减少；体外表现出 B 细胞活化降低；并显示 KLH 暴露后 BLV 前病毒载量增加。此外，BLV+奶牛的外周血CD45R0(+)gamma delta(+) T细胞数量减少，并且体外产生IL4的T细胞的比例更高。总而言之，我们的结果表明，BLV+ 奶牛的 B 细胞和 T 细胞免疫均被破坏，并且即使在初次免疫暴露后，也可以在 BLV+ 奶牛中检测到抗原特异性缺陷。
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(+)gamma delta(+) 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.