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

<p>An increasing number of studies has indicated that the immune system plays important roles in the pathogenesis of Parkinson&#39;s disease. However, little is known about the contribution of adaptive immune responses in Parkinson&#39;s disease. Here, we performed comprehensive integrative analyses of single-cell transcriptome and immune profiling of the blood of 8 Parkinson&#39;s patients and 13 healthy controls as well as the cerebrospinal fluid of 6 Parkinson&#39;s patients, 4 Alzheimer&#39;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&#39;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&#39;s patients compared to controls, suggesting their cytotoxic roles in Parkinson&#39;s disease. Finally, we screened putative TCR-antigen pairs that existed in both blood and cerebrospinal fluid of patients with Parkinson&#39;s disease. These results reveal an adaptive immune response in the blood and cerebrospinal fluid of Parkinson&#39;s disease and provide novel evidence of clonal, antigen-experienced T cells patrolling in the blood and cerebrospinal fluid of Parkinson&#39;s disease.</p>