Cytomegalovirus drives Vδ2neg γδ T cell inflation in many healthy virus carriers with increasing age.
Cytomegalovirus drives Vδ2neg γδ T cell inflation in many healthy virus carriers with increasing age.
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DOI：
10.1111/cei.12297
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发表时间：
2014-06
影响因子：
4.6
通讯作者：
Khan N
中科院分区：
文献类型：
--
作者：
Alejenef A;Pachnio A;Halawi M;Christmas SE;Moss PA;Khan N
巨细胞病毒（CMV）通常导致终身无症状感染，但随着时间的推移可以扭曲免疫谱。最近的报道描述了在健康和免疫功能低下的CMV携带者中Vδ2neg γδ T细胞的选择性扩增。先前研究表明，老年CMV携带者的病毒特异性CD8+和CD4+ T细胞反应显著增加，这可能是由慢性刺激驱动的，我们假设Vδ2neg γδ T细胞也可能随着年龄的增长而扩大。我们的研究结果表明，在所有年龄组中，与cmv血清阴性对照相比，cmv血清阳性健康人的v δ2负γδ T细胞显著增加。老年组差异最显著（P < 0.0001）。此外，虽然在CMV血清阴性的供者中，v δ2负γδ T-细胞包括初始细胞和记忆细胞，但在CMV携带者中，高度分化的效应记忆细胞是主要表型，而在CMV血清阳性的老年人中，初始细胞的数量显著减少。虽然在表型上类似于传统的cmv特异性T细胞，但在这些个体中，v δ2负γδ T细胞与cmv特异性CD4+或CD8+ T细胞频率的大小变化无关，并且不具有cmv特异性CD4+和CD8+ T细胞所显示的离体即时效应功能。然而，在短期培养后，Vδ2neg γδ T细胞表现出效应T细胞功能，这表明激活需要额外的条件。总之，Vδ2neg γδ T细胞在许多老年CMV携带者中扩增，表明CMV在健康个体中进一步扭曲淋巴细胞亚群。正如其他人报道的，Vδ2neg γδ T细胞对肿瘤细胞具有共同的反应性，γδ T细胞亚群的组成也可能与老年人患癌症的风险有关。
Cytomegalovirus (CMV) usually causes lifelong asymptomatic infection, but over time can distort immune profiles. Recent reports describe selective expansion of Vδ2neg γδ T cells in healthy and immunocompromised CMV carriers. Having shown previously that virus-specific CD8+ and CD4+ T cell responses are increased significantly in elderly CMV carriers, probably driven by chronic stimulation, we hypothesized that Vδ2neg γδ T cells may also be expanded with age. Our results show that Vδ2neg γδ T cells are increased significantly in CMV-seropositive healthy individuals compared to CMV-seronegative controls in all age groups. The differences were most significant in older age groups (P < 0·0001). Furthermore, while Vδ2neg γδ T- cells comprise both naive and memory cells in CMV-seronegative donors, highly differentiated effector memory cells are the dominant phenotype in CMV carriers, with naive cells reduced significantly in numbers in CMV-seropositive elderly. Although phenotypically resembling conventional CMV-specific T cells, Vδ2neg γδ T cells do not correlate with changes in magnitude of CMV-specific CD4+ or CD8+ T cell frequencies within those individuals, and do not possess ex-vivo immediate effector function as shown by CMV-specific CD4+ and CD8+ T cells. However, after short-term culture, Vδ2neg γδ T cells demonstrate effector T cell functions, suggesting additional requirements for activation. In summary, Vδ2neg γδ T cells are expanded in many older CMV carriers, demonstrating a further level of lymphocyte subset skewing by CMV in healthy individuals. As others have reported shared reactivity of Vδ2neg γδ T cells towards tumour cells, the composition of γδ T cell subsets may also have implications for risk of developing cancer in elderly people.
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