Integrative analyses of single-cell transcriptome and immune profiling reveal clonal expansion of T cells in the blood and cerebrospinal fluid of Parkinson's disease

An increasing number of studies has indicated that the immune system plays important roles in the pathogenesis of Parkinson's disease. However, little is known about the contribution of adaptive immune responses in Parkinson's disease. Here, we performed comprehensive integrative analyses of single-cell transcriptome and immune profiling of the blood of 8 Parkinson's patients and 13 healthy controls as well as the cerebrospinal fluid of 6 Parkinson's patients, 4 Alzheimer's patients, 5 mild cognitive impairment (MCI) patients and 9 healthy controls. In total, 22 T cell subsets with distinct functions and clonalities were identified from 121,402 T cells. We observed significant clonal expansion of effector CD8+ T cells in Parkinson's patients, which formed a gradient of transcriptional states from central memory CD8+ T cells to early effector CD8+ T cells followed by terminal effector CD8+ T cells. Shared TCRs in this progression suggest TCRs may be involved in the state transition of CD8+ T cells stimulated by antigens. Notably, we also found that a group of clonally expanded cytotoxic CD4+ T cells were significantly increased in Parkinson's patients compared to controls, suggesting their cytotoxic roles in Parkinson's disease. Finally, we screened putative TCR-antigen pairs that existed in both blood and cerebrospinal fluid of patients with Parkinson's disease. These results reveal an adaptive immune response in the blood and cerebrospinal fluid of Parkinson's disease and provide novel evidence of clonal, antigen-experienced T cells patrolling in the blood and cerebrospinal fluid of Parkinson's disease.