Deficient CD4+ T cell priming and regression of CD8+T cell functionality in virus-infected mice lacking a normal B cell compartment
Deficient CD4+ T cell priming and regression of CD8+T cell functionality in virus-infected mice lacking a normal B cell compartment
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DOI：
10.4049/jimmunol.171.9.4733
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发表时间：
2003-11-01
影响因子：
4.4
通讯作者：
Thomsen, AR
中科院分区：
文献类型：
--
作者：
Christensen, JP;Kauffmann, SO;Thomsen, AR
在这项研究中，我们调查的状态T细胞介导的免疫B细胞缺陷（B-/-）小鼠感染两株淋巴细胞性脉络丛脑膜炎病毒，其持续的能力显着不同。在感染更持久病毒的B-/-C57 BL小鼠中，最初产生的病毒特异性CD 8（+）T细胞在性质上与野生型小鼠相似。然而，尽管细胞数量随着时间的推移得到很好的维持，但产生细胞因子的能力迅速受损。在类似感染的B-/- BALB/c小鼠中，病毒特异性CD 8（+）T细胞完全缺失，表明宿主基因型影响T细胞缺陷的严重程度。在感染持续时间较短的病毒的B-/-C57 BL小鼠中，CD 8（+）T细胞功能障碍并不明显，尽管它明显存在。最重要的是，功能失调的CD 8（+）T细胞的出现明显先于可检测到的病毒的复发，这表明T细胞缺陷不仅仅是由于B-/-小鼠不能产生中和抗体而导致的病毒积聚引起的继发事件。与CD 8（+）T细胞的初始反应几乎与野生型小鼠相同相反，病毒特异性CD 4（+）T细胞的启动在感染任一病毒株的B-/-小鼠中明显受损。因此，我们的研究结果表明，B细胞在抗病毒免疫中发挥重要作用，不仅作为抗体生产者，而且在促进最佳和持续的T细胞反应。T细胞缺陷可能导致B-/-小鼠中病毒感染的慢性过程。
In this study, we investigate the state of T cell-mediated immunity in B cell-deficient (B-/-) mice infected with two strains of lymphocytic choriomeningitis virus known to differ markedly in their capacity to persist. In B-/- C57BL mice infected with the more persisting virus, virus-specific CD8(+) T cells are initially generated that are qualitatively similar to those in wild-type mice. However, although cell numbers are well sustained over time, the capacity to produce cytokines is rapidly impaired. In similarly infected B-/- BALB/c mice, virus-specific CD8(+) T cells are completely deleted, indicating that host genotype influences the severity of the T cell defect. In B-/- C57BL mice infected with the less persisting virus, CD8(+) T cell dysfunction was not as pronounced, although it was clearly present. Most importantly, the appearance of dysfunctional CD8(+) T cells clearly precedes recrudescence of detectable virus, indicating that the T cell defect is not simply a secondary event due to virus buildup resulting from the failure of B-/- mice to produce neutralizing Abs. In contrast with CD8(+) T cells, which initially respond almost as in wild-type mice, the priming of virus-specific CD4(+) T cells was markedly impaired in B-/- mice infected with either virus strain. Thus, our results indicate that B cells play an important role in antiviral immunity not only as Ab producers, but also in promoting an optimal and sustained T cell response. The T cell defects are likely to contribute to the chronic course of viral infection in B-/- mice.