Cell子刊：复旦大学金俊团队等揭示老年人免疫力下降背后的分子与细胞生物学机制

Core Viewpoint - The research highlights the role of extracellular proteins in supporting T cell immunity, particularly in the context of aging and its impact on immune response [2][4][7]. Group 1: Research Findings - The study published in Cell Reports reveals that even healthy elderly individuals with normal albumin levels (>25g/L) may experience limited T cell functionality during acute viral infections due to relatively lower albumin concentrations [2]. - Activated T cells can internalize extracellular proteins like albumin, degrade them in lysosomes, and release free amino acids such as leucine, which are crucial for maintaining mTORC1 activity and cytokine production, thereby enhancing antiviral and antitumor immunity [4][5]. - The transcription factor TFE3 plays a central regulatory role in this process, with its expression being specifically upregulated during T cell activation, promoting lysosomal biogenesis and protein degradation capabilities [4][5]. Group 2: Clinical Implications - The clinical significance of this pathway has been validated in elderly lung cancer patients, where tumor-infiltrating CD8⁺ T cells showed significantly reduced lysosomal degradation capacity and cytokine secretion compared to middle-aged patients [5]. - The study suggests that the activation of mTORC1 is regulated by both rapid signals from extracellular free amino acids and sustained amino acid signals from lysosomal degradation of extracellular proteins, which may influence the differentiation balance between effector T cells and memory T cells [5][7]. - The functional impairment of elderly T cells arises from both intrinsic lysosomal dysfunction and extrinsic declines in plasma albumin levels [5][7].