Differentiation and regulation of CD4⁺ T cell subsets in Parkinson's disease

Parkinson's disease (PD) is the second most common neurodegenerative disease, and its hallmark pathological features are the loss of dopaminergic (DA) neurons in the midbrain substantia nigra pars compacta (SNpc) and the accumulation of alpha-synuclein (α-syn). It has been shown that the integrity of the blood-brain barrier (BBB) is damaged in PD patients, and a large number of infiltrating T cells and inflammatory cytokines have been detected in the cerebrospinal fluid (CSF) and brain parenchyma of PD patients and PD animal models, including significant change in the number and proportion of different CD4⁺ T cell subsets. This suggests that the neuroinflammatory response caused by CD4⁺ T cells is an important risk factor for the development of PD. Here, we systematically review the differentiation of CD4⁺ T cell subsets, and focus on describing the functions and mechanisms of different CD4⁺ T cell subsets and their secreted cytokines in PD. We also summarize the current immunotherapy targeting CD4⁺ T cells with a view to providing assistance in the diagnosis and treatment of PD.