引言
在人类免疫缺陷病毒（human immunodeficiency virus，HIV）感染中，CD8+T细胞对于病毒的清除至关重要【1】。因此，CD8+T细胞生物学动态与HIV感染患者息息相关。在慢性感染和肿瘤中，持续的抗原刺激诱导耗竭性T细胞（exhausted T cell，Tx）的产生【2】。TX的典型特征是由TOX等转录因子驱动的转录组和表观组重塑介导的效应功能减弱和抑制性受体的高表达【2】。值得注意的是，TOX不仅表达于Tx，也会表达于部分多功能效应记忆性T细胞，有时甚至与TCF-1共表达【3,4】，呈现干细胞样特性。研究表明，在大多数HIV感染患者中，HIV-特异性CD8+T细胞耗竭分子表达增加与高病毒载量和疾病进展相关【3,5】。在HIV感染患者外周血中，部分HIV-特异性CD8+T细胞中检测到TCF-1和TOX共表达【4】。作为HIV病毒存在和复制的主要位点，淋巴结内CD8+T细胞的表型和功能状态对于治疗策略的改善和设计至关重要。
近日，美国埃默里大学国家灵长动物研究中心微生物与免疫学部Mirko Paiardini研究团队在Nature Immunology杂志发表了题为Distinct SIV-specific CD8+ T cells in the lymph node exhibit simultaneous effector and stem-like profiles and are associated with limited SIV persistence的研究文章。这项研究通过流式、质谱、scRNA-seq和TCR-seq等分析在淋巴结内鉴定一群具有干细胞特性中间效应功能的SIV-特异性TOXhiTCF1+CD39+CD8+T细胞，该细胞倾向于淋巴滤泡定居并与靶细胞靠近，且能分化为终末效应细胞参与SIV病毒控制，为SIV/HIV感染提供新的免疫治疗靶点。
参考文献
1. David R, Collins., Gaurav D, Gaiha., Bruce D, Walker.(2020). CD8+ T cells in HIV control, cure and prevention. Nat Rev Immunol, 20(8), 0. doi:10.1038/s41577-020-0274-9
2. Christian U, Blank., W Nicholas, Haining., Werner, Held., Patrick G, Hogan., Axel, Kallies., Enrico, Lugli., et al. (2019). Defining 'T cell exhaustion'. Nat Rev Immunol, 19(11), 0. doi:10.1038/s41577-019-0221-9
3. Jean-Christophe, Beltra., Sasikanth, Manne., Mohamed S, Abdel-Hakeem., Makoto, Kurachi., et al. (2020). Developmental Relationships of Four Exhausted CD8+ T Cell Subsets Reveals Underlying Transcriptional and Epigenetic Landscape Control Mechanisms. Immunity, 52(5), 0. doi:10.1016/j.immuni.2020.04.014
4. Takuya, Sekine., André, Perez-Potti., Son, Nguyen., Jean-Baptiste, Gorin., Vincent H, Wu., Emma, et al. (2020). TOX is expressed by exhausted and polyfunctional human effector memory CD8+ T cells. Sci Immunol, 5(49), 0. doi:10.1126/sciimmunol.aba7918
5. David R, Collins., Jonathan M, Urbach., Zachary J, Racenet., Umar, Arshad., Karen A, Power., et al. (2021). Functional impairment of HIV-specific CD8+ T cells precedes aborted spontaneous control of viremia. Immunity, 54(10), 0. doi:10.1016/j.immuni.2021.08.007
6. Se Jin, Im., Masao, Hashimoto., Michael Y, Gerner., Junghwa, Lee., Haydn T, Kissick., Matheus C, et al. (2016). Defining CD8+ T cells that provide the proliferative burst after PD-1 therapy. Nature, 537(7620), 0. doi:10.1038/nature19330
7. Morgan A, Reuter., Perla M, Del Rio Estrada., Marcus, Buggert., Constantinos, Petrovas., Sara, et al. (2017). HIV-Specific CD8(+) T Cells Exhibit Reduced and Differentially Regulated Cytolytic Activity in Lymphoid Tissue. Cell Rep, 21(12), 0. doi:10.1016/j.celrep.2017.11.075
8. Son, Nguyen., Claire, Deleage., Samuel, Darko., Amy, Ransier., Duc P, Truong., Divyansh, Agarwal., et al. (2019). Elite control of HIV is associated with distinct functional and transcriptional signatures in lymphoid tissue CD8(+) T cells. Sci Transl Med, 11(523), 0. doi:10.1126/scitranslmed.aax4077
9. Constantinos, Petrovas., Sara, Ferrando-Martinez., Michael Y, Gerner., Joseph P, Casazza., Amarendra, et al. (2017). Follicular CD8 T cells accumulate in HIV infection and can kill infected cells in vitro via bispecific antibodies. Sci Transl Med, 9(373), 0. doi:10.1126/scitranslmed.aag2285
https://doi.org/10.1038/s41590-024-01875-0
责编|探索君
排版|探索君
来源|BioArt
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