Schmitt Michaela E R, Sitte Selina, Voehringer David
Department of Infection Biology, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) , Erlangen , Germany.
Front Immunol. 2016 Dec 21;7:622. doi: 10.3389/fimmu.2016.00622. eCollection 2016.
Lymphopenic conditions lead to expansion of memory-like T cells (T), which develop from naïve T cells by spontaneous proliferation. T cells are often increased in the elderly population, AIDS patients, and patients recovering from radio- or chemotherapy. At present, it is unclear whether T cells can efficiently respond to foreign antigen and participate in antiviral immunity. To address this question, we analyzed the immune response during acute low-dose infection with lymphocytic choriomeningitis virus-WE in T cell lymphopenic CD4Cre/R-diphtheria toxin alpha (DTA) mice in which most peripheral T cells show a T phenotype. On day 8 after infection, the total number of effector T cells and polyfunctional IFN-γ and TNF-α producing CD8 T cells were three- to fivefold reduced in CD4Cre/R-DTA mice as compared to controls. Viral clearance and the humoral immune response were severely impaired in CD4Cre/R-DTA mice although CTLs efficiently killed transferred target cells . Transfer of naïve CD4 T cells but not anti-PD-L1 blockade restored the expansion of antigen-specific polyfunctional CD8 T cells and resulted in lower viral titers. This finding indicates that under lymphopenic conditions endogenous CD4 T cell lack the capacity to promote expansion of CTLs. However, CD8 T cells retain sufficient functional plasticity to participate in antiviral immunity in the presence of appropriate help by fully functional CD4 T cells. This capacity might be exploited to develop treatments for improvement of CD8 T cell functions under various clinical settings of lymphopenia.
淋巴细胞减少症会导致记忆样T细胞（T细胞）扩增，这些T细胞由初始T细胞通过自发增殖产生。在老年人群、艾滋病患者以及接受放疗或化疗后康复的患者中，T细胞数量通常会增加。目前尚不清楚这些T细胞是否能够有效应对外来抗原并参与抗病毒免疫。为了解决这个问题，我们分析了淋巴细胞脉络丛脑膜炎病毒-WE低剂量急性感染期间，T细胞淋巴细胞减少的CD4Cre/R-白喉毒素α（DTA）小鼠的免疫反应，在这种小鼠中，大多数外周T细胞呈现T细胞表型。感染后第8天，与对照组相比，CD4Cre/R-DTA小鼠中效应T细胞以及产生多功能干扰素-γ和肿瘤坏死因子-α的CD8 T细胞总数减少了三到五倍。尽管细胞毒性T淋巴细胞（CTL）能够有效杀伤转移的靶细胞，但CD4Cre/R-DTA小鼠的病毒清除和体液免疫反应严重受损。转移初始CD4 T细胞而非抗程序性死亡配体1（PD-L1）阻断可恢复抗原特异性多功能CD8 T细胞的扩增，并导致病毒滴度降低。这一发现表明，在淋巴细胞减少的条件下，内源性CD4 T细胞缺乏促进CTL扩增的能力。然而，在功能完全正常的CD4 T细胞提供适当帮助的情况下，CD8 T细胞保留了足够的功能可塑性以参与抗病毒免疫。这种能力可用于开发在各种淋巴细胞减少的临床情况下改善CD8 T细胞功能的治疗方法。
