T cells producing GM-CSF and IL-13 are enriched in the cerebrospinal fluid of relapsing MS patients

Laura Ghezzi, Department of Neurology, School of Medicine, Washington University, St. Louis, MO, USA/Centro Dino Ferrari, University of Milan, Milan, Italy/Fondazione IRCCS Ca' Granda, Ospedale Policlinico, Milan, Italy.
Claudia Cantoni, Department of Neurology, School of Medicine, Washington University, St. Louis, MO, USA.Follow
Francesca Cignarella, Department of Neurology, School of Medicine, Washington University, St. Louis, MO, USA.
Bryan Bollman, Department of Neurology, School of Medicine, Washington University, St. Louis, MO, USA.
Anne H. Cross, Department of Neurology, School of Medicine, Washington University, St. Louis, MO, USA/Hope Center for Neurological Disorders, School of Medicine, Washington University, St. Louis, MO, USA.
Amber Salter, Division of Biostatistics, School of Medicine, Washington University, St. Louis, MO, USA.
Daniela Galimberti, Department of Biomedical, Surgical and Dental Science, University of Milan, Milan, Italy/Centro Dino Ferrari, University of Milan, Milan, Italy/Fondazione IRCCS Ca' Granda, Ospedale Policlinico, Milan, Italy.
Marina Cella, Department of Pathology and Immunology, School of Medicine, Washington University, St. Louis, MO, USA/Hope Center for Neurological Disorders, School of Medicine, Washington University, St. Louis, MO, USA.
Laura Piccio, Department of Neurology, School of Medicine, Washington University, St. Louis, MO, USA/Hope Center for Neurological Disorders, School of Medicine, Washington University, St. Louis, MO, USA/Brain and Mind Centre, University of Sydney, Sydney, New South Wales, Australia.

Document Type

Article

Abstract

BACKGROUND: Multiple sclerosis (MS) is a central nervous system (CNS) autoimmune demyelinating disease. Its pathogenesis involves humoral and cellular immunity, with production of pro- and anti-inflammatory cytokines by T cells. OBJECTIVE: To analyze the cytokine profile of cerebrospinal fluid (CSF) T cells in patients with relapsing-remitting MS (RRMS) and non-inflammatory controls. METHODS: T cell cytokine production was analyzed by flow cytometry in CSF samples collected from 34 untreated RRMS patients and 20 age-matched controls. Immunofluorescence studies were performed in spinal cord MS active lesions. RESULTS: Percentages of CSF-derived IL-17A, IL-17A/IL-22, and IL-17A/GM-CSF producing T cells were significantly higher in RRMS patients compared to controls. Percentages of T cells producing IFN-γ were lower in RRMS patients compared to controls. Patients in relapse showed higher percentages of CD4 T cells producing IL-13 and GM-CSF compared to patients in remission. We found a positive correlation between percentages of IL-13 T cells and the Expanded Disability Status Scale (EDSS; ρ = 0.5;  < 0.05). Meningeal IL-13-producing T cells were detected in spinal cord MS active lesions. CONCLUSION: We observed differences in IL-17, IL-22, and IFN-γ production by CSF T cells in RRMS versus controls and a positive correlation between IL-13-producing T cells and EDSS in RRMS patients.

Keywords

Multiple sclerosis, T cells, cerebrospinal fluid, cytokines

Medical Subject Headings

Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Interleukin-13; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Recurrence; T-Lymphocytes

Publication Date

9-1-2020

Publication Title

Multiple sclerosis (Houndmills, Basingstoke, England)

E-ISSN

1477-0970

Volume

26

Issue

10

First Page

1172

Last Page

1186

PubMed ID

31237799

Digital Object Identifier (DOI)

10.1177/1352458519852092

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