老化细胞积累已被认为参与老化相关疾病的发病机制，包括癌症。防止老化人体器官中老化细胞积聚的机制尚不清楚。在这里，我们证明了病毒免疫轴控制了老年人皮肤中老化成纤维细胞的积累。与年轻人的皮肤相比，老年皮肤中老化成纤维细胞增加。然而，在老年人中随着年龄的增长，它们并没有增加。CXCL9和细胞毒性CD4+ T细胞（CD4 CTL）的增加与老年皮肤中老化成纤维细胞的减少显著相关。老化成纤维细胞表达人类白细胞抗原类II（HLA-II）和人类巨细胞病毒糖蛋白B（HCMV-gB），成为直接的CD4 CTL靶标。皮肤驻留CD4 CTL以HLA-II依赖方式清除了HCMV-gB+老化成纤维细胞，而HCMV-gB激活了人体皮肤中的CD4 CTL。总之，我们的研究结果表明HCMV在老化细胞中重新活化，CD4 CTL可以通过识别HCMV-gB抗原直接消除老化细胞。 版权所有©2023 Elsevier Inc.。

Senescent cell accumulation has been implicated in the pathogenesis of aging-associated diseases, including cancer. The mechanism that prevents the accumulation of senescent cells in aging human organs is unclear. Here, we demonstrate that a virus-immune axis controls the senescent fibroblast accumulation in the human skin. Senescent fibroblasts increased in old skin compared with young skin. However, they did not increase with advancing age in the elderly. Increased CXCL9 and cytotoxic CD4+ T cells (CD4 CTLs) recruitment were significantly associated with reduced senescent fibroblasts in the old skin. Senescent fibroblasts expressed human leukocyte antigen class II (HLA-II) and human cytomegalovirus glycoprotein B (HCMV-gB), becoming direct CD4 CTL targets. Skin-resident CD4 CTLs eliminated HCMV-gB+ senescent fibroblasts in an HLA-II-dependent manner, and HCMV-gB activated CD4 CTLs from the human skin. Collectively, our findings demonstrate HCMV reactivation in senescent cells, which CD4 CTLs can directly eliminate through the recognition of the HCMV-gB antigen.Copyright © 2023 Elsevier Inc. All rights reserved.