Dose-dependent changes in influenza virus-infected dendritic cells result in increased allogeneic T-cell proliferation at low, but not high, doses of virus
Dose-dependent changes in influenza virus-infected dendritic cells result in increased allogeneic T-cell proliferation at low, but not high, doses of virus
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DOI：
10.1128/jvi.74.12.5460-5469.2000
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发表时间：
2000-06-01
影响因子：
5.4
通讯作者：
Eichelberger, MC
中科院分区：
文献类型：
--
作者：
Oh, S;McCaffery, JM;Eichelberger, MC
在感染甲型流感病毒的急性期，淋巴细胞减少的程度与疾病的严重程度相关。由于树突状细胞(DC)与T细胞相互作用时启动了免疫反应，因此我们建立了一个体外系统来检测流感病毒感染对DC功能的影响。我们的结果表明，同种异体T细胞的增殖依赖于A/PR/8/34感染DC的剂量，在低而不是高的感染多样性时，反应增强。在高病毒剂量下缺乏增强作用主要不是由于DC凋亡率的增加，而是需要病毒复制和神经氨酸酶(NA)活性。DC之间或DC和T细胞之间形成的簇也依赖于病毒剂量。这种细胞相互作用的改变可能会对抗高剂量PR8感染的DC的T细胞增殖，因为DC之间的接触增加导致T细胞被排斥，增强的同种异体反应性T细胞反应通过中和转化生长因子β1(TGFβ1)恢复。高剂量PR8感染的DC释放的病毒颗粒上的NA可能激活TGF-β1，未来的研究将确定TGF-β1改变体外T细胞反应的机制，并解决这种细胞因子在严重疾病中观察到的淋巴细胞减少的作用。
During the acute phase of infection with influenza A virus, the degree of lymphopenia correlates with severity of disease. Factors that contribute to T-cell activation during influenza virus infection may contribute to this observation, Since the immune response is initiated when dendritic cells (DC) interact with T cells, we have established an in vitro system to examine the effects of influenza virus infection on DC function. Our results show that allogeneic T-cell proliferation was dependent on the dose of A/PR/8/34 used to infect DC, with enhanced responses at low, but not high, multiplicities of infection. The lack of enhancement at high virus doses was not primarily due to the increased rate of DC apoptosis, but required viral replication and neuraminidase (NA) activity. Clusters that formed between DC or between DC and T cells were also dependent on the viral dose. This change in cellular interaction may oppose T-cell proliferation in response to DC infected with high doses of PR8, since the increased contact between DC resulted in the exclusion of T cells, The enhanced alloreactive T-cell response was restored by neutralization of transforming growth factor beta 1 (TGF beta 1) It is likely that NA present on viral particles released from DC infected with high doses of PR8 activates TGF-beta 1, Future studies will determine the mechanism by which TGF-beta 1 modifies the in vitro T-cell response and address the contribution of this cytokine to the lymphopenia observed in severe disease.