Murine γ-Herpesvirus 68 limits naturally occurring CD4+ CD25+ T regulatory cell activity following infection
Murine γ-Herpesvirus 68 limits naturally occurring CD4+ CD25+ T regulatory cell activity following infection
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DOI：
10.4049/jimmunol.177.7.4670
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发表时间：
2006-10-01
影响因子：
4.4
通讯作者：
Bost, Kenneth L.
中科院分区：
文献类型：
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作者：
Gasper-Smith, Nancy;Marriott, Ian;Bost, Kenneth L.
在微生物感染期间，自然产生的CD4(+)CD25(+)T调节细胞可以抑制保护性宿主反应，或者它们可以限制病原体诱导的炎症反应。这些细胞所扮演的特殊角色似乎取决于正在研究的感染源。伽马疱疹病毒是一种有效的病原体，以其诱发淋巴增生性疾病和在宿主中建立潜伏期的能力而闻名。然而，还没有研究调查在感染这些病毒期间自然产生的CD4(+)CD25(+)T调节细胞的重要性。使用伽马疱疹病毒感染的小鼠模型，小鼠伽玛疱疹病毒68(Gamma HV-68)，我们惊讶地发现，随着病毒潜伏期的增加和疾病白细胞增多期的进展，CD4(+)CD25(+)T调节细胞转录本FoxP3的水平继续下降。与这些结果一致的是，FoxP3蛋白表达的下降遵循类似的动力学。除了这种调节性T细胞标记物的表达减少外，我们还观察到从伽马HV-68感染动物分离的这些细胞中CD4(+)CD25(+)T调节性细胞活性降低。体外感染γHV-68的树突状细胞不改变正常的CD4(+)CD25(+)调节性T细胞在刺激后限制CD4(+)Th细胞增殖的能力。综上所述，这些研究表明，在这种病毒感染的单核细胞增多症样阶段，CD4(+)CD25(+)T调节细胞的存在和活性降低。这些自然发生的T调节细胞功能的改变可能有助于解释宿主免疫反应的失调，这种失调允许随着病毒潜伏期的建立而不受控制地扩大白细胞。
During microbial infections, naturally occurring CD4(+)CD25(+) T regulatory cells can suppress protective host responses or they can limit pathogen-induced inflammatory responses. The particular role played by these cells seems to depend upon the infectious agent being investigated. gamma-Herpesviruses are efficacious pathogens which are well-known for their ability to induce lymphoproliferative disease and to establish latency in the host. However, no studies have investigated the importance of naturally occurring CD4(+)CD25(+) T regulatory cells during infection with these viruses. Using the murine model of gamma-herpesvirus infection, murine gamma-herpesvirus 68 (gamma HV-68), we were surprised to find that levels of the CD4(+)CD25(+) T regulatory cell transcript, FoxP3, continued to decrease as viral latency increased and as the leukocytosis phase of the disease progressed. Consistent with these results, the decrease in FoxP3 protein expression followed similar kinetics. Along with the reduced expression of this regulatory T cell marker, we also observed diminished CD4(+)CD25(+) T regulatory cell activity in these cells isolated from, gamma HV-68-infected animals. Dendritic cells infected in vitro with gamma HV-68 did not alter the ability of normal CD4(+)CD25(+) regulatory T cells to limit the proliferation of CD4(+) Th cells following stimulation. Taken together, these studies demonstrate a decreased presence and activity of CD4(+)CD25(+) T regulatory cells during the mononucleosis-like phase of this viral infection. These alterations in naturally occurring T regulatory cell function may help to explain the dysregulation of the host's immune response which allows the uncontrolled expansion of leukocytes as viral latency is established.