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Sci Immunol. 2020 Sep 18;5(51). doi: 10.1126/sciimmunol.abb8786.

Transcriptomic and clonal characterization of T cells in the human central nervous system.

Science immunology

Jenna L Pappalardo, Le Zhang, Maggie K Pecsok, Kelly Perlman, Chrysoula Zografou, Khadir Raddassi, Ahmad Abulaban, Smita Krishnaswamy, Jack Antel, David van Dijk, David A Hafler

Affiliations

  1. Departments of Neurology and Immunobiology, Yale School of Medicine, New Haven, CT 06511, USA.
  2. Montreal Neurologic Institute, Montreal, Quebec, Canada.
  3. Departments of Genetics and Computer Science, Yale School of Medicine, New Haven, CT 06511, USA.
  4. Departments of Internal Medicine (Cardiology), Cardiovascular Research Center, and Computer Science, New Haven, CT 06511, USA. [email protected] [email protected].
  5. Departments of Neurology and Immunobiology, Yale School of Medicine, New Haven, CT 06511, USA. [email protected] [email protected].
  6. Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

PMID: 32948672 PMCID: PMC8567322 DOI: 10.1126/sciimmunol.abb8786

Abstract

T cells provide critical immune surveillance to the central nervous system (CNS), and the cerebrospinal fluid (CSF) is thought to be a main route for their entry. Further characterization of the state of T cells in the CSF in healthy individuals is important for understanding how T cells provide protective immune surveillance without damaging the delicate environment of the CNS and providing tissue-specific context for understanding immune dysfunction in neuroinflammatory disease. Here, we have profiled T cells in the CSF of healthy human donors and have identified signatures related to cytotoxic capacity and tissue adaptation that are further exemplified in clonally expanded CSF T cells. By comparing profiles of clonally expanded T cells obtained from the CSF of patients with multiple sclerosis (MS) and healthy donors, we report that clonally expanded T cells from the CSF of patients with MS have heightened expression of genes related to T cell activation and cytotoxicity.

Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

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