Generalized immune activation as a direct result of activated CD4+ T cell killing
Generalized immune activation as a direct result of activated CD4+ T cell killing
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DOI：
10.1186/jbiol194
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发表时间：
2009-11-27
期刊：
影响因子：
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通讯作者：
Kassiotis, George
中科院分区：
文献类型：
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作者：
Marques, Rute;Williams, Adam;Kassiotis, George
背景资料：除了进行性CD4（+）T细胞免疫缺陷，HIV感染的特点是广泛的免疫激活，被认为是由于微生物暴露的增加而导致免疫力下降。结果：在这里，我们报告说，在无病毒的小鼠模型，条件消融活化的CD4（+）T细胞，免疫缺陷病毒的目标，加速其营业额和产生CD4（+）T细胞免疫缺陷。更重要的是，活化的CD4（+）T细胞杀伤也导致全身性免疫活化，这可归因于调节性CD4（+）T细胞不足，并且可通过调节性CD4（+）T细胞重建来预防。该模型中的免疫激活独立于微生物暴露而发展。此外，肠道上皮完整性条件性破坏的小鼠中的微生物易位影响骨髓但不影响T细胞稳态。尽管小鼠中活化的CD4+ T细胞的消融和肠上皮完整性的破坏都不能完全再现人类中HIV相关免疫功能障碍的各个方面，但活化的CD4+ T细胞的消融，而不是肠上皮完整性的破坏，近似于HIV感染中的两个关键免疫改变：CD4+ T细胞免疫缺陷和全身免疫激活。因此，我们提出活化的CD4+ T细胞杀伤作为HIV感染中免疫缺陷和活化的共同病因。
Background: In addition to progressive CD4(+) T cell immune deficiency, HIV infection is characterized by generalized immune activation, thought to arise from increased microbial exposure resulting from diminishing immunity.Results: Here we report that, in a virus-free mouse model, conditional ablation of activated CD4(+) T cells, the targets of immunodeficiency viruses, accelerates their turnover and produces CD4(+) T cell immune deficiency. More importantly, activated CD4(+) T cell killing also results in generalized immune activation, which is attributable to regulatory CD4(+) T cell insufficiency and preventable by regulatory CD4(+) T cell reconstitution. Immune activation in this model develops independently of microbial exposure. Furthermore, microbial translocation in mice with conditional disruption of intestinal epithelial integrity affects myeloid but not T cell homeostasis.Conclusions: Although neither ablation of activated CD4+ T cells nor disruption of intestinal epithelial integrity in mice fully reproduces every aspect of HIV-associated immune dysfunction in humans, ablation of activated CD4+ T cells, but not disruption of intestinal epithelial integrity, approximates the two key immune alterations in HIV infection: CD4+ T cell immune deficiency and generalized immune activation. We therefore propose activated CD4+ T cell killing as a common etiology for both immune deficiency and activation in HIV infection.