The CSF in neurosarcoidosis contains consistent clonal expansion of CD8 T cells, but not CD4 T cells

Authors

• Michael A. Paley, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, United States of America. Electronic address: paleym@wustl.edu.
• Brandi J. Baker, Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, United States of America.
• S Richard Dunham, Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, United States of America.
• Nicole Linskey, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, United States of America.
• Claudia Cantoni, Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, United States of America.Follow
• Kenneth Lee, Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, United States of America.
• Lynn M. Hassman, Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110, United States of America.
• Jennifer Laurent, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, United States of America.
• Elisha D. Roberson, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, United States of America; Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110, United States of America.
• David B. Clifford, Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, United States of America.
• Wayne M. Yokoyama, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, United States of America. Electronic address: yokoyama@wustl.edu.

Document Type

Article

Abstract

The tissue-specific drivers of neurosarcoidosis remain poorly defined. To identify cerebrospinal fluid (CSF) specific, antigen-driven T and B cell responses, we performed single-cell RNA sequencing of CSF and blood cells from neurosarcoid participants coupled to T and B cell receptor sequencing. In contrast to pulmonary sarcoidosis, which is driven by CD4 T cells, we found CD8 T cell clonal expansion enriched in the neurosarcoid CSF. These CSF-enriched CD8 T cells were composed of two subsets with differential expression of EBI2, CXCR3, and CXCR4. Lastly, our data suggest that IFNγ signaling may distinguish neurosarcoidosis from other neurological disorders.

Keywords

Interferon, Neurosarcoidosis, Sarcoidosis, Single-cell RNA sequencing, T cells, TCR sequencing

Medical Subject Headings

CD4-Positive T-Lymphocytes (metabolism); CD8-Positive T-Lymphocytes (metabolism); Central Nervous System Diseases (cerebrospinal fluid); Humans; Sarcoidosis (cerebrospinal fluid)

Publication Date

6-15-2022

Publication Title

Journal of neuroimmunology

E-ISSN

1872-8421

Volume

367

First Page

577860

PubMed ID

35405431

Digital Object Identifier (DOI)

10.1016/j.jneuroim.2022.577860

Recommended Citation

Paley, Michael A.; Baker, Brandi J.; Dunham, S Richard; Linskey, Nicole; Cantoni, Claudia; Lee, Kenneth; Hassman, Lynn M.; Laurent, Jennifer; Roberson, Elisha D.; Clifford, David B.; and Yokoyama, Wayne M., "The CSF in neurosarcoidosis contains consistent clonal expansion of CD8 T cells, but not CD4 T cells" (2022). Translational Neuroscience. 2351.
https://scholar.barrowneuro.org/neurobiology/2351