Laura Ghezzi1, Claudia Cantoni2, Francesca Cignarella2, Bryan Bollman2, Anne H Cross3, Amber Salter4, Daniela Galimberti5, Marina Cella6, Laura Piccio7. 1. 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. 2. Department of Neurology, School of Medicine, Washington University, St. Louis, MO, USA. 3. 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. 4. Division of Biostatistics, School of Medicine, Washington University, St. Louis, MO, USA. 5. 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. 6. 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. 7. 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.
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; p < 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.
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; p < 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.
Entities:
Keywords:
Multiple sclerosis; T cells; cerebrospinal fluid; cytokines
Authors: Alin Laurentiu Tatu; Anca Arbune; Valentin Chioncel; Elena Niculet; Thomas Nadasdy; Carmen Bobeica; Alina Viorica Iancu; Caterina Dumitru; Valentin Tudor Popa; Nicolas Kluger; Victor Gabriel Clatici; Claudiu Ionut Vasile; Cristian Onisor; Alexandru Nechifor Journal: J Inflamm Res Date: 2022-09-08