美国哈佛医学院Shadmehr Demehri等研究人员合作发现，细胞毒性CD4⁺T细胞通过靶向巨细胞病毒抗原消除衰老细胞。2023年3月30日，国际知名学术期刊《细胞》发表了这一成果。

研究人员证明了病毒-免疫轴控制着人类皮肤中衰老成纤维细胞的积累。与年轻皮肤相比，老年皮肤中的衰老成纤维细胞有所增加。然而，它们并没有随着老年人年龄的增长而增加。CXCL9和细胞毒性CD4⁺T细胞（CD4 CTL）招募的增加与老年皮肤中衰老成纤维细胞的减少明显相关。衰老的成纤维细胞表达人类白细胞抗原II类（HLA-II）和人类巨细胞病毒糖蛋白B（HCMV-gB），成为CD4 CTL的直接靶标。皮肤常驻的CD4 CTL以HLA-II依赖性的方式消除了HCMV-gB⁺的衰老成纤维细胞，而HCMV-gB激活了人类皮肤的CD4 CTL。

总之，这些发现表明HCMV在衰老细胞中重新激活，CD4 CTL可以通过识别HCMV-gB抗原直接消除这些细胞。

据介绍，衰老细胞的积累与衰老相关疾病（包括癌症）的发病机制有关。防止衰老的人体器官中的衰老细胞积累的机制尚不清楚。

附：英文原文

Title: Cytotoxic CD4+ T cells eliminate senescent cells by targeting cytomegalovirus antigen

Author: Tatsuya Hasegawa, Tomonori Oka, Heehwa G. Son, Valeria S. Oliver-García, Marjan Azin, Thomas M. Eisenhaure, David J. Lieb, Nir Hacohen, Shadmehr Demehri

Issue&Volume: 2023/03/30

Abstract: Senescent cell accumulation has been implicated in the pathogenesis of aging-associateddiseases, including cancer. The mechanism that prevents the accumulation of senescentcells in aging human organs is unclear. Here, we demonstrate that a virus-immune axiscontrols the senescent fibroblast accumulation in the human skin. Senescent fibroblastsincreased in old skin compared with young skin. However, they did not increase withadvancing age in the elderly. Increased CXCL9 and cytotoxic CD4+ T cells (CD4 CTLs) recruitment were significantly associated with reduced senescentfibroblasts in the old skin. Senescent fibroblasts expressed human leukocyte antigenclass II (HLA-II) and human cytomegalovirus glycoprotein B (HCMV-gB), becoming directCD4 CTL targets. Skin-resident CD4 CTLs eliminated HCMV-gB+ senescent fibroblasts in an HLA-II-dependent manner, and HCMV-gB activated CD4 CTLsfrom the human skin. Collectively, our findings demonstrate HCMV reactivation in senescentcells, which CD4 CTLs can directly eliminate through the recognition of the HCMV-gBantigen.

DOI: 10.1016/j.cell.2023.02.033

Source: https://www.cell.com/cell/fulltext/S0092-8674(23)00211-8