人类巨细胞病毒(hCMV)特异性记忆 T 细胞的单细胞转录组和 T 细胞抗原受体分析揭示了 CD8+ - 和 CD4+ - 细胞毒性 T 细胞的效应因子和前效应因子。

IF 4.9 3区 医学 Q2 IMMUNOLOGY
Immunology Pub Date : 2024-03-19 DOI:10.1111/imm.13783
Raunak Kar, Somdeb Chattopadhyay, Anjali Sharma, Kirti Sharma, Shreya Sinha, Gopalakrishnan Aneeshkumar Arimbasseri, Veena S. Patil
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引用次数: 0

摘要

潜伏的人类巨细胞病毒(hCMV)感染会对免疫力低下的人造成重新激活和疾病发生的严重威胁。虽然 T 细胞是 hCMV 感染保护性免疫反应的核心,但目前还缺乏对参与 hCMV 免疫的不同 T 细胞亚群的详细描述。在这里,我们以无偏见的方式,通过分析与 T 细胞抗原受体 (TCR) 复合物配对的单细胞转录组,以单细胞分辨率鉴定了从血清阳性人类供体中分离出来的 8000 多个 hCMV 反应性外周记忆 T 细胞。hCMV 反应性 T 细胞具有高度异质性,由不同的发育和功能记忆 T 细胞亚群组成,如长期记忆前体和效应细胞、T 辅助细胞-17、T 调节细胞 (TREGs) 以及 CD4 和 CD8 来源的细胞毒性 T 淋巴细胞 (CTLs)。hCMV 特异性 TREG 除了富集已知的抑制功能分子外,还富集了干扰素反应特征基因组。hCMV 特异性 CTL 有两种类型,即前效应细胞和类效应细胞。hCMV特异性CD4-CTLs和CD8-CTLs在前效应器和效应器集群中的共聚表明它们之间有共同的转录组特征。细胞毒性集群的巨大 TCR 克隆扩增表明,它们在对 CMV 的保护性免疫反应中起着主导作用。该研究揭示了 hCMV 特异性记忆 T 细胞的异质性,揭示了许多功能亚群,对更好地理解 hCMV 特异性 T 细胞免疫具有潜在的意义。这些数据可作为设计疫苗和疗法的知识基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Single-cell transcriptomic and T cell antigen receptor analysis of human cytomegalovirus (hCMV)-specific memory T cells reveals effectors and pre-effectors of CD8+- and CD4+-cytotoxic T cells

Single-cell transcriptomic and T cell antigen receptor analysis of human cytomegalovirus (hCMV)-specific memory T cells reveals effectors and pre-effectors of CD8+- and CD4+-cytotoxic T cells

Single-cell transcriptomic and T cell antigen receptor analysis of human cytomegalovirus (hCMV)-specific memory T cells reveals effectors and pre-effectors of CD8+- and CD4+-cytotoxic T cells

Latent human cytomegalovirus (hCMV) infection can pose a serious threat of reactivation and disease occurrence in immune-compromised individuals. Although T cells are at the core of the protective immune response to hCMV infection, a detailed characterization of different T cell subsets involved in hCMV immunity is lacking. Here, in an unbiased manner, we characterized over 8000 hCMV-reactive peripheral memory T cells isolated from seropositive human donors, at a single-cell resolution by analysing their single-cell transcriptomes paired with the T cell antigen receptor (TCR) repertoires. The hCMV-reactive T cells were highly heterogeneous and consisted of different developmental and functional memory T cell subsets such as, long-term memory precursors and effectors, T helper-17, T regulatory cells (TREGs) and cytotoxic T lymphocytes (CTLs) of both CD4 and CD8 origin. The hCMV-specific TREGs, in addition to being enriched for molecules known for their suppressive functions, showed enrichment for the interferon response signature gene sets. The hCMV-specific CTLs were of two types, the pre-effector- and effector-like. The co-clustering of hCMV-specific CD4-CTLs and CD8-CTLs in both pre-effector as well as effector clusters suggest shared transcriptomic signatures between them. The huge TCR clonal expansion of cytotoxic clusters suggests a dominant role in the protective immune response to CMV. The study uncovers the heterogeneity in the hCMV-specific memory T cells revealing many functional subsets with potential implications in better understanding of hCMV-specific T cell immunity. The data presented can serve as a knowledge base for designing vaccines and therapeutics.

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来源期刊
Immunology
Immunology 医学-免疫学
CiteScore
11.90
自引率
1.60%
发文量
175
审稿时长
4-8 weeks
期刊介绍: Immunology is one of the longest-established immunology journals and is recognised as one of the leading journals in its field. We have global representation in authors, editors and reviewers. Immunology publishes papers describing original findings in all areas of cellular and molecular immunology. High-quality original articles describing mechanistic insights into fundamental aspects of the immune system are welcome. Topics of interest to the journal include: immune cell development, cancer immunology, systems immunology/omics and informatics, inflammation, immunometabolism, immunology of infection, microbiota and immunity, mucosal immunology, and neuroimmunology. The journal also publishes commissioned review articles on subjects of topical interest to immunologists, and commissions in-depth review series: themed sets of review articles which take a 360° view of select topics at the heart of immunological research.
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