The contribution of Chlamydia-specific CD8⁺ T cells to upper genital tract pathology.
The contribution of Chlamydia-specific CD8⁺ T cells to upper genital tract pathology.
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DOI：
10.1038/icb.2015.74
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发表时间：
2016-02
影响因子：
4
通讯作者：
Murthy AK
中科院分区：
文献类型：
--
作者：
Vlcek KR;Li W;Manam S;Zanotti B;Nicholson BJ;Ramsey KH;Murthy AK
生殖器衣原体感染导致严重的上生殖道病理在一个子集未经治疗的妇女。我们之前已经证明，产生TNF-α的CD8+ T细胞在雌性小鼠的衣原体上生殖道病理中起着重要作用。此外，我们在OT-1转基因（OT-1）小鼠中观察到最小的衣原体输卵管病理，其中CD8+ T细胞库仅限于识别卵清蛋白肽Ova257-264，这表明非衣原体特异性CD8+ T细胞可能与衣原体发病无关。在目前的研究中，我们评估了抗原特异性CD8+ T细胞是否介导衣原体病理。将野生型C57BL/6J （WT）、WT -1小鼠和WT - CD8+ T细胞充满的OT-1小鼠（1×106细胞/小鼠）经阴道感染5 × 104 IFU/小鼠。血清总抗衣原体抗体和脾脏总抗衣原体IFN-γ和TNF-α反应在三组动物之间具有可比性。然而，从纯化的OT-1小鼠脾脏CD8+ T细胞中产生的衣原体特异性IFN-γ和TNF-α很少，而在WT CD8+ T细胞充满的OT-1小鼠中的反应与WT动物相当。阴道衣原体清除率在三组小鼠之间具有可比性。重要的是，OT-1小鼠输卵管和子宫角病变的发生率和严重程度显著降低，而在WT CD8+ T细胞充满的OT-1小鼠中，输卵管和子宫角病变的发生率和严重程度恢复到WT水平。总之，这些结果表明衣原体特异性CD8+ T细胞在上生殖道病理中起着重要作用。
Genital chlamydial infections lead to severe upper reproductive tract pathology in a subset of untreated women. We demonstrated previously that TNF-α producing CD8+ T cells contribute significantly to chlamydial upper genital tract pathology in female mice. Additionally, we observed minimal chlamydial oviduct pathology develops in OT-1 transgenic (OT-1) mice, wherein CD8+ T cell repertoire is restricted to recognition of the ovalbumin peptide Ova257–264, suggesting that non-Chlamydia-specific CD8+ T cells may not be responsible for chlamydial pathogenesis. In the current study, we evaluated whether antigen-specific CD8+ T cells mediate chlamydial pathology. Groups of wild type C57BL/6J (WT), OT-1 mice, and OT-1 mice replete with WT CD8+ T cells (1×106 cells/mouse intravenously) were infected intravaginally with C. muridarum (5 × 104 IFU/mouse). Serum total anti-Chlamydia antibody and total splenic anti-Chlamydia IFN-γ and TNF-α responses were comparable among the three groups of animals. However, Chlamydia-specific IFN-γ and TNF-α production from purified splenic CD8+ T cells of OT-1 mice was minimal, whereas responses in OT-1 mice replete with WT CD8+ T cells were comparable to those in WT animals. Vaginal chlamydial clearance was comparable between the three groups of mice. Importantly, the incidence and severity of oviduct and uterine horn pathology was significantly reduced in OT-1 mice but reverted to WT levels in OT-1 mice replete with WT CD8+ T cells. Collectively, these results demonstrate that Chlamydia-specific CD8+ T cells contribute significantly to upper genital tract pathology.