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Absence of PD-1 expression on TFH and TFC cell subsets correlates with severity of multiple sclerosis.

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Title: Absence of PD-1 expression on TFH and TFC cell subsets correlates with severity of multiple sclerosis.
Authors: Lopes LMF; Department of Microbiology and Parasitology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil; Post-graduate Program in Microbiology, University of the State of Rio de Janeiro, Rio de Janeiro, Brazil., Hygino J; Department of Microbiology and Parasitology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil; Post-graduate Program in Microbiology, University of the State of Rio de Janeiro, Rio de Janeiro, Brazil., Cafasso MOS; Department of Microbiology and Parasitology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil; Post-graduate Program in Microbiology, University of the State of Rio de Janeiro, Rio de Janeiro, Brazil., Sacramento PM; Department of Microbiology and Parasitology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil; Post-graduate Program in Microbiology, University of the State of Rio de Janeiro, Rio de Janeiro, Brazil., Sales MC; Department of Microbiology and Parasitology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil; Post-graduate Program in Microbiology, University of the State of Rio de Janeiro, Rio de Janeiro, Brazil., Kasahara TM; Department of Microbiology and Parasitology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil; Post-graduate Program in Microbiology, University of the State of Rio de Janeiro, Rio de Janeiro, Brazil., Andrade RM; Department of General Medicine, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil., de Souza Lopes LC; Post-graduate Program in Neurology and Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil., de Azevedo CA; Post-graduate Program in Neurology and Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil., Vasconcelos CC; Post-graduate Program in Neurology and Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil., de Melo Bento CA; Department of Microbiology and Parasitology, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil; Post-graduate Program in Neurology and Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil; Department of General Medicine, Federal University of the State of Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address: cbento@unirio.br.
Source: Journal of neuroimmunology [J Neuroimmunol] 2026 Oct; Vol. 419, pp. 579012. Date of Electronic Publication: 2026 Jun 27.
Publication Type: Journal Article
Language: English
Journal Info: Publisher: Elsevier/North-Holland Country of Publication: Netherlands NLM ID: 8109498 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-8421 (Electronic) Linking ISSN: 01655728 NLM ISO Abbreviation: J Neuroimmunol Subsets: MEDLINE
Imprint Name(s): Original Publication: [Amsterdam] : Elsevier/North-Holland, c1981-
MeSH Terms: Programmed Cell Death 1 Receptor*/biosynthesis , Programmed Cell Death 1 Receptor*/metabolism , Multiple Sclerosis*/immunology , Multiple Sclerosis*/pathology , CD8-Positive T-Lymphocytes*/metabolism , CD8-Positive T-Lymphocytes*/immunology, Humans ; Male ; Female ; Adult ; Severity of Illness Index ; Middle Aged
Abstract: Follicular CD4+ T (TFH) cells have been implicated in the pathogenesis of multiple sclerosis (MS). However, studies evaluating follicular CD8+ T (TFC) cells and the relationship between TFH/TFC cells with clinical MS parameters are lacking. Here, the frequency of circulating TFH/TFC cells from healthy and MS subjects was determined by cytometry according the expression of PD-1, CXCR3, CCR6, IL-21, IFN-γ and IL-17 by CXCR5+CD4+/CD8+T-cells. The plasma CXCL13 and NfL levels were quantified by ELISA. The degree of neurological disability and brain lesions were determined by EDSS score and magnetic resonance imaging, respectively. Relapse occurrence was evaluated during 1-year follow-up. Our results demonstrated that PD-1+IL-21+TFH-cell subsets (TFH1, TFH17.1 and TFH17) frequency and the percentage of PD-1+IL-21+TFC17.1 and PD-1-IL-21+TFH17.1/TFC17.1 cells were higher in the MS than in the control group. Different IL-17-expressing PD-1-IL-21+TFH/TFC cell subsets positively correlated with plasma CXCL13 and NfL levels. Also, circulating PD-1-IL-21+TFH17/TFC17 directly correlated with neurological disabilities. While radiological activity of disease positively correlated with percentage of PD-1-IL-21+TFH17.1/TFH17 cells and PD-1-IL-21+TFC1/TFC17.1/TFC17 cells, clinical activity of MS was associated with both elevated levels of CXCL13 and NfL and the frequencies of PD-1-IL-21+TFH17.1/TFH17 and PD-1-IL-21+TFC1/TFC17.1 cells. In summary, our findings suggest that PD-1-TFH/TFC cells able to produce IL-21, IFN-γ and IL-17 could be a signature of MS severity.
(Copyright © 2026. Published by Elsevier B.V.)
Competing Interests: Declaration of competing interest The authors declare having no conflict of interest.
Contributed Indexing: Keywords: CXCL13; Multiple sclerosis; T(FC) cells; T(FH) cells
Substance Nomenclature: 0 (Programmed Cell Death 1 Receptor)
0 (PDCD1 protein, human)
Entry Date(s): Date Created: 20260708 Date Completed: 20260808 Latest Revision: 20260808
Update Code: 20260809
DOI: 10.1016/j.jneuroim.2026.579012
PMID: 42419041
Database: MEDLINE
Description
ISSN:1872-8421
DOI:10.1016/j.jneuroim.2026.579012