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淋巴结将性别偏向性免疫衰老与受损的抗原识别联系起来。

Lymph nodes link sex-biased immune aging to compromised antigen recognition.

作者信息

Menzel Lutz, Zschummel Maria, O'Melia Meghan J, Zhou Hengbo, Lei Pin-Ji, Liu Lingshan, Sen Debattama R, Munn Lance L, Padera Timothy P

出版信息

bioRxiv. 2025 May 2:2025.02.11.637693. doi: 10.1101/2025.02.11.637693.

DOI:10.1101/2025.02.11.637693
PMID:39990447
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11844512/
Abstract

A diverse naive CD8 T cell repertoire is essential to provide broad protection against infection and cancer. Aging diminishes naive T cells, reducing potential diversity and leading to lymph node contraction. Here, we revealed that this decline occurs earlier in males, resulting in significant sex differences in immunity during middle age. Earlier in life, naive CD8 T cells in males become virtual memory cells prone to premature senescence. Due to androgen-driven thymic atrophy in males, naive CD8 T cells are insufficiently replenished. Therapeutic thymus rejuvenation via testosterone ablation restored naive CD8 T cells in lymph nodes of middle-aged male mice, leading to enhanced tumor recognition. These findings show the crucial role of sex and age on lymph node T cell repertoires and suggest potential strategies to restore immune function in males during aging.

摘要

多样化的初始CD8 T细胞库对于提供针对感染和癌症的广泛保护至关重要。衰老会减少初始T细胞，降低潜在的多样性并导致淋巴结萎缩。在此，我们揭示这种下降在男性中出现得更早，导致中年时期免疫方面存在显著的性别差异。在生命早期，男性的初始CD8 T细胞会变成易于过早衰老的虚拟记忆细胞。由于雄激素驱动的男性胸腺萎缩，初始CD8 T细胞无法得到充分补充。通过睾酮消融进行的治疗性胸腺 rejuvenation 恢复了中年雄性小鼠淋巴结中的初始CD8 T细胞，从而增强了肿瘤识别能力。这些发现表明性别和年龄对淋巴结T细胞库的关键作用，并提出了在衰老过程中恢复男性免疫功能的潜在策略。

（注：“rejuvenation”这个词在原文语境中可能是个特定的专业术语，暂时保留英文未翻译，你可根据实际情况补充准确中文释义）

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/966d/12498716/932bfeb33af2/nihpp-2025.02.11.637693v3-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/966d/12498716/6c88057959cc/nihpp-2025.02.11.637693v3-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/966d/12498716/e6fd53bd0976/nihpp-2025.02.11.637693v3-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/966d/12498716/bffabff9ced5/nihpp-2025.02.11.637693v3-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/966d/12498716/581bd8baa275/nihpp-2025.02.11.637693v3-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/966d/12498716/d9ba418b88d9/nihpp-2025.02.11.637693v3-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/966d/12498716/932bfeb33af2/nihpp-2025.02.11.637693v3-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/966d/12498716/6c88057959cc/nihpp-2025.02.11.637693v3-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/966d/12498716/e6fd53bd0976/nihpp-2025.02.11.637693v3-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/966d/12498716/bffabff9ced5/nihpp-2025.02.11.637693v3-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/966d/12498716/581bd8baa275/nihpp-2025.02.11.637693v3-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/966d/12498716/d9ba418b88d9/nihpp-2025.02.11.637693v3-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/966d/12498716/932bfeb33af2/nihpp-2025.02.11.637693v3-f0006.jpg

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本文引用的文献

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Age-Associated Contraction of Tumor-Specific T Cells Impairs Antitumor Immunity.年龄相关的肿瘤特异性 T 细胞收缩损害抗肿瘤免疫。
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