CMV Status Drives Distinct Trajectories of CD4+ T Cell Differentiation.
CMV Status Drives Distinct Trajectories of CD4+ T Cell Differentiation.
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DOI：
10.3389/fimmu.2021.620386
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发表时间：
2021
影响因子：
7.3
通讯作者：
Larsen CP
中科院分区：
文献类型：
--
作者：
Zhang W;Morris AB;Peek EV;Karadkhele G;Robertson JM;Kissick HT;Larsen CP
巨细胞病毒（CMV）是最常见的机会致病菌之一，并且仍然是塑造个体免疫系统的最有影响力的已知参数。因此，CMV感染诱导的T细胞可能对随后的免疫应答产生长期影响。越来越多的证据表明，在过去的细菌和病毒感染过程中产生的记忆T细胞可以与不相关的病原体（包括移植抗原）发生交叉反应，并可以改变对新生感染、疫苗、癌症或排斥反应的反应。因此，有必要仔细检查CMV引起的T细胞应答，以了解它们在未来主要免疫事件中的潜在有益或有害作用。我们使用高维流式细胞术和单细胞多组学测序对CMV血清阳性健康个体中CD 4 + T细胞的分布、表型、TCR库和转录组进行了详细探索，结果显示CMV血清阳性具有高度显著的年龄无关效应，导致CD 4+幼稚T细胞减少，CD 4+效应记忆T细胞和CD 45 RA+效应记忆T细胞扩增。这些诱导的CD 4+效应记忆T细胞经历特定的分化轨迹，产生具有细胞毒性功能和TCR寡克隆性的CD 57 + CD 27-CD 28-CD 244 + CD 4 + T细胞亚群，用于与巨细胞病毒的最佳受控共存。通过基因集富集分析，我们发现这个亚群类似于病毒特异性CD 8 + T细胞和T细胞，这些细胞在使用他克莫司和贝拉西普（一种选择性共刺激阻断剂）的患者中介导急性排斥反应。总之，这些数据表明，由巨细胞病毒诱导的记忆性CD 4 + T细胞是通过不同的分化程序形成的，以获得细胞毒性功能，并且可能对采用共刺激阻断免疫抑制方案的移植患者有害。
Cytomegalovirus (CMV) is one of the most commonly recognized opportunistic pathogens and remains the most influential known parameter in shaping an individual’s immune system. As such, T cells induced by CMV infection could have a long-term impact on subsequent immune responses. Accumulating evidence indicates that memory T cells developed during past bacterial and viral infection can cross-react with unrelated pathogens, including transplant antigens, and can alter responses to de novo infections, vaccines, cancers, or rejection. Therefore, careful examination of T cell responses elicited by CMV is warranted to understand their potentially beneficial or harmful roles in future major immune events. Our detailed exploration of the distribution, phenotype, TCR repertoire and transcriptome of CD4+ T cells within CMV seropositive healthy individuals using high-dimensional flow cytometry and single cell multi-omics sequencing reveals that CMV seropositivity has highly significant age-independent effects, leading to a reduction in CD4+ naïve T cells and an expansion of CD4+ effector memory T cells and CD45RA+ effector memory T cells. These induced CD4+ effector memory T cells undergo a specific differentiation trajectory resulting in a subpopulation of CD57+CD27-CD28-CD244+ CD4+ T cells with cytotoxic function and TCR oligoclonality for optimal controlled coexistence with cytomegalovirus. Through gene set enrichment analysis, we found that this subpopulation is similar to virus-specific CD8+ T cells and T cells that mediate acute rejection in patients using tacrolimus and belatacept, a selective costimulation blocker. Together, these data suggest that memory CD4+ T cells induced by cytomegalovirus are formed via a distinct differentiation program to acquire cytotoxic function and can be potentially detrimental to transplant patients adopting costimulation blockade immunosuppressive regimen.
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影响因子：
3
作者：
Haining WN;Angelosanto J;Brosnahan K;Ross K;Hahn C;Russell K;Drury L;Norton S;Nadler L;Stegmaier K
通讯作者：
Stegmaier K
DOI：
10.1111/ajt.13613
发表时间：
2016-04
期刊：
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子：
--
作者：
Espinosa J;Herr F;Tharp G;Bosinger S;Song M;Farris AB 3rd;George R;Cheeseman J;Stempora L;Townsend R;Durrbach A;Kirk AD
通讯作者：
Kirk AD
影响因子：
64.5
作者：
Brodin P;Jojic V;Gao T;Bhattacharya S;Angel CJ;Furman D;Shen-Orr S;Dekker CL;Swan GE;Butte AJ;Maecker HT;Davis MM
通讯作者：
Davis MM
影响因子：
4.4
作者：
Arens, Ramon;Wang, Peng;Benedict, Chris A.
通讯作者：
Benedict, Chris A.
影响因子：
5.4
作者：
Johnson, Susan;Eller, Michael;Streeck, Hendrik
通讯作者：
Streeck, Hendrik