Neural Regeneration Research ›› 2026, Vol. 21 ›› Issue (5): 1864-1889.doi: 10.4103/NRR.NRR-D-24-01539

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Neuroinflammation in neurodegenerative diseases: Focusing on the mediation of T lymphocytes

Ke Li1 , Rongsha Chen1 , Ruohua Wang1, 2, Wenhui Fan1 , Ninghui Zhao1, 3, *, Zhongshan Yang4, *, Jinyuan Yan1, *   

  1. 1 Experiment Center, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, China;  2 Department of Blood Transfusion, Yunnan Cancer Hospital, Kunming, Yunnan Province, China;  3 Department of Neurosurgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, China;  4 Yunnan Provincial Key Laboratory of Molecular Biology for Sino Medicine, Yunnan University of Traditional Chinese Medicine, Kunming, Yunnan Province, China
  • Online:2026-05-15 Published:2025-08-21
  • Contact: Ninghui Zhao, MD, zhaoninghui@kmmu.edu.cn; Zhongshan Yang, PhD, yangzhongshan@ynucm.edu.cn; Jinyuan Yan, PhD, yanjinyuan@kmmu.edu.cn.
  • Supported by:
    This work was supported by Yunnan Provincial Science and Technology Department, Nos. 202403AC100007 (to NZ), 202301AY070001-239 (to JY); Yunnan Revitalization Talent Support Program, Nos. 2019-069 (to ZY) and 2019-300 (to JY); the National Natural Science Foundation of China, Nos. 32260196 (to JY); a grant from Kunming Medical University, No. 2024S085 (to KL).

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Abstract: Neurodegenerative diseases are a group of illnesses characterized by the gradual deterioration of the central nervous system, leading to a decline in patients’ cognitive, motor, and emotional abilities. Neuroinflammation plays a significant role in the progression of these diseases. However, there is limited research on therapeutic approaches to specifically target neuroinflammation. The role of T lymphocytes, which are crucial mediators of the adaptive immune response, in neurodegenerative diseases has been increasingly recognized. This review focuses on the involvement of T lymphocytes in the neuroinflammation associated with neurodegenerative diseases. The pathogenesis of neurodegenerative diseases is complex, involving multiple mechanisms and pathways that contribute to the gradual degeneration of neurons, and T cells are a key component of these processes. One of the primary factors driving neuroinflammation in neurodegenerative diseases is the infiltration of T cells and other neuroimmune cells, including microglia, astrocytes, B cells, and natural killer cells. Different subsets of CD4+ T cells, such as Th1, Th2, Th17, and regulatory T cells, can differentiate into various cell types and perform distinct roles within the neuroinflammatory environment of neurodegenerative diseases. Additionally, CD8+ T cells, which can directly regulate immune responses and kill target cells, also play several important roles in neurodegenerative diseases. Clinical trials investigating targeted T cell therapies for neurodegenerative diseases have shown that, while some patients respond positively, others may not respond as well and may even experience adverse effects. Targeting T cells precisely is challenging due to the complexity of immune responses in the central nervous system, which can lead to undesirable side effects. However, with new insights into the pathophysiology of neurodegenerative diseases, there is hope for the establishment of a solid theoretical foundation upon which innovative treatment strategies that target T cells can be developed in the future.

Key words: Alzheimer’s disease, amyotrophic lateral sclerosis, CD4+ T cell, CD8+ T cell, helper T cell, multiple sclerosis, neurodegenerative diseases, neuroinflammation, Parkinson’s disease, regulatory T cell