Methods to investigate intrathecal adaptive immunity in neurodegeneration

Hamilton Oh, Olivia Leventhal, Divya Channappa, Victor W. Henderson, Tony Wyss-Coray, Benoit Lehallier, David Gate*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Background: Cerebrospinal fluid (CSF) provides basic mechanical and immunological protection to the brain. Historically, analysis of CSF has focused on protein changes, yet recent studies have shed light on cellular alterations. Evidence now exists for involvement of intrathecal T cells in the pathobiology of neurodegenerative diseases. However, a standardized method for long-term preservation of CSF immune cells is lacking. Further, the functional role of CSF T cells and their cognate antigens in neurodegenerative diseases are largely unknown. Results: We present a method for long-term cryopreservation of CSF immune cells for downstream single cell RNA and T cell receptor sequencing (scRNA-TCRseq) analysis. We observe preservation of CSF immune cells, consisting primarily of memory CD4+ and CD8+ T cells. We then utilize unbiased bioinformatics approaches to quantify and visualize TCR sequence similarity within and between disease groups. By this method, we identify clusters of disease-associated, antigen-specific TCRs from clonally expanded CSF T cells of patients with neurodegenerative diseases. Conclusions: Here, we provide a standardized approach for long-term storage of CSF immune cells. Additionally, we present unbiased bioinformatic approaches that will facilitate the discovery of target antigens of clonally expanded T cells in neurodegenerative diseases. These novel methods will help improve our understanding of adaptive immunity in the central nervous system.

Original languageEnglish (US)
Article number3
JournalMolecular neurodegeneration
Volume16
Issue number1
DOIs
StatePublished - Dec 2021
Externally publishedYes

Keywords

  • Adaptive immunity
  • Antigen
  • CSF
  • Cerebrospinal fluid cells
  • Intrathecal cells
  • Neurodegeneration
  • T cell receptor (TCR)
  • T cells

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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