Changes of T lymphocyte subpopulations and their roles in predicting the risk of Parkinson’s disease

Abstract

T lymphocytes are involved in the pathogenesis of Parkinson’s disease (PD), while the heterogeneity of T-cell subpopulations remains elusive. In this study, we analyzed up to 22 subpopulations of T lymphocytes in 115 PD patients and 60 matched healthy controls (HC) using flow cytometry. We found that PD patients exhibited decreased naïve CD8+ T cells (CD3+ CD8+ CD45RA+ CD45RO−) and increased late-differentiated CD4+ T cells (CD3+ CD4+ CD28− CD27−), compared to HC, which were not affected by anti-parkinsonism medication administration. The proportion of naïve CD8+ T cells in PD patients was positively correlated with their severity of autonomic dysfunction and psychiatric complications, but negatively associated with the severity of rapid eye movement and sleep behavior disorder. The proportion of late-differentiated CD4+ T cells was negatively correlated with the onset age of the disease. We further developed individualized PD risk prediction models with high reliability and accuracy on the base of the T lymphocyte subpopulations. These data suggest that peripheral cellular immunity is disturbed in PD patients, and changes in CD8+ T cells and late-differentiated CD4+ T cells are representative and significant. Therefore, we recommend naïve CD8 + and late-differentiated CD4+ T cells as candidates for multicentric clinical study and pathomechanism study of PD.

Neuron-derived exosomes trigger a PD-L1-mediated broad suppression of T cells in Parkinson’s disease

“…For example, our nding that activation of puri ed CD4 + T cells is signi cantly reduced by NDEs from A53T-syn models may offer a mechanism underlying disease progression since a reduction of activated CD4 + T cells has been associated with the advancement of PD [10,11,49]. Our nding that A53T-syn Exo suppresses both naïve and matured CD8 + T supports previous studies reporting decreases of naïve CD8 + T cells and cytotoxic CD8 + T cells in PD [9,49,50]. Several studies have noted a decrease of Th1 cells and Th1-promoting transcription factors including T-bet, STAT3, and STAT4 in PD patients [14,51], which is consistent with our nding that A53T-syn NDEs reduce T-bet level and suppress Th1 differentiation.…”

CD8+ T cell depletion prevents neuropathology in a mouse model of globoid cell leukodystrophy

“…In conclusion, our findings increase the fundamental understanding of how GLD pathology occurs and suggest salient insights that may support novel therapeutic approaches to treat GLD. Furthermore, these data have potential relevance for other neurological diseases in which CD8 + T cells have been implicated, yet their origins remain enigmatic, such as Alzheimer’s disease ( Altendorfer et al, 2022 ; Gate et al, 2020 ), Parkinson’s disease ( Williams-Gray et al, 2018 ; He et al, 2022 ), or amyotrophic lateral sclerosis ( Campisi et al, 2022 ; Rentzos et al, 2012 ). Hence, we propose that the development of CD8 + T cells in this model represents a unique opportunity to study the natural development of CD8 + T cell responses that appear to target the CNS.…”

CD8+ T cells in brain injury and neurodegeneration

“…Similar to AD, many studies have reported an alteration in T lymphocytes in the peripheral blood (PBs) and CSF of PD patients (Baba et al, 2005;He et al, 2022;Heming et al, 2022). Early studies showed an increased or decreased ratio of CD4 to CD8 + T cells in the PBs and CSF of PD patients (Hisanaga et al, 2001;Baba et al, 2005).…”

“…PD Infiltration PB or CSF of PD patients: CD4 to CD8 ratio changes (He et al, 2022;Fu et al, 2023); decreased number (Baek et al, 2016); CD8 + T cell terminal effector phenotype (Marsh et al, 2016), with high expression of TNFα Heming et al, 2022) and show immunosenescence (Hisanaga et al, 2001;Chen et al, 2021). Brain tissue of PD patients: significant infiltration in the SN (Williams-Gray et al, 2018;Kouli et al, 2021;Jiang et al, 2023).…”

“…Early studies showed an increased or decreased ratio of CD4 to CD8 + T cells in the PBs and CSF of PD patients (Hisanaga et al, 2001;Baba et al, 2005). Further mapping indicates that the number of naïve CD8 + T cells is reduced (He et al, 2022) and that a large population of CD8 + T cells continuously progress from central memory to terminal effector T cells in the blood and CFS of PD patients based on single-cell transcriptome expression combined with TCR-sequencing . Moreover, these CD8 + T cells are activated and show high expression of TNFα (Chen et al, 2021;Jiang et al, 2023).…”