Bovine leukemia virus reduces anti-viral cytokine activities and NK cytotoxicity by inducing TGF-β secretion from regulatory T cells.
Bovine leukemia virus reduces anti-viral cytokine activities and NK cytotoxicity by inducing TGF-β secretion from regulatory T cells.
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DOI：
10.1002/iid3.93
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发表时间：
2016-03
期刊：
影响因子：
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通讯作者：
Ohashi K
中科院分区：
文献类型：
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作者：
Ohira K;Nakahara A;Konnai S;Okagawa T;Nishimori A;Maekawa N;Ikebuchi R;Kohara J;Murata S;Ohashi K
CD4+CD25highFoxp3+ T 细胞可抑制导致自身免疫和/或炎症性疾病的过度免疫反应，并维持宿主免疫稳态。然而，据报道，CD4+CD25highFoxp3+ T 细胞通过过度抑制某些慢性感染中的免疫反应而导致疾病进展。在这项研究中，对感染牛白血病病毒 (BLV) 的牛进行了 CD4+CD25highFoxp3+ T 细胞的动力学和功能分析，该病毒已报告了免疫抑制特征。在最初的实验中，与未感染的牛相比，BLV 感染的牛产生的 Th1 细胞因子 IFN-γ 和 TNF-α 减少，并且随着疾病进展，产生 IFN-γ 或 TNF-α 的 CD4+ T 细胞数量减少。相比之下，NK 细胞产生的 IFN-γ 与受感染牛体内的 BLV 前病毒载量呈负相关。此外，在持续性淋巴细胞增多症阶段，NK 细胞毒性被抑制，如溶细胞蛋白穿孔素的低表达所示。与此同时，CD4+CD25highFoxp3+ T 细胞总数和 TGF-β+ 细胞百分比增加，表明 TGF-β 在 CD4+ T 细胞和 NK 细胞的功能下降中发挥作用。在进一步的实验中，重组牛 TGF-β 抑制 CD4+ T 细胞产生 IFN-γ 和 TNF-α 以及培养细胞中的 NK 细胞毒性。这些数据表明，来自 CD4+CD25highFoxp3+ T 细胞的 TGF-β 具有免疫抑制作用，有助于 BLV 感染期间疾病进展和机会性感染的发展。
CD4+CD25highFoxp3+ T cells suppress excess immune responses that lead to autoimmune and/or inflammatory diseases, and maintain host immune homeostasis. However, CD4+CD25highFoxp3+ T cells reportedly contribute to disease progression by over suppressing immune responses in some chronic infections. In this study, kinetic and functional analyses of CD4+CD25highFoxp3+ T cells were performed in cattle with bovine leukemia virus (BLV) infections, which have reported immunosuppressive characteristics. In initial experiments, production of the Th1 cytokines IFN‐γ and TNF‐α was reduced in BLV‐infected cattle compared with uninfected cattle, and numbers of IFN‐γ or TNF‐α producing CD4+ T cells decreased with disease progression. In contrast, IFN‐γ production by NK cells was inversely correlated with BLV proviral loads in infected cattle. Additionally, during persistent lymphocytosis disease stages, NK cytotoxicity was depressed as indicated by low expression of the cytolytic protein perforin. Concomitantly, total CD4+CD25highFoxp3+ T cell numbers and percentages of TGF‐β+ cells were increased, suggesting that TGF‐β plays a role in the functional declines of CD4+ T cells and NK cells. In further experiments, recombinant bovine TGF‐β suppressed IFN‐γ and TNF‐α production by CD4+ T cells and NK cytotoxicity in cultured cells. These data suggest that TGF‐β from CD4+CD25highFoxp3+ T cells is immunosuppressive and contributes to disease progression and the development of opportunistic infections during BLV infection.