Brain Antigens Stimulate Proliferation of T Lymphocytes With a Pathogenic Phenotype in Multiple Sclerosis Patients

Authors

Assaf Gottlieb
Hoai Phuong T Pham
John William Lindsey

Publication Date

1-1-2022

Journal

Frontiers in Immunology

Abstract

A method to stimulate T lymphocytes with a broad range of brain antigens would facilitate identification of the autoantigens for multiple sclerosis and enable definition of the pathogenic mechanisms important for multiple sclerosis. In a previous work, we found that the obvious approach of culturing leukocytes with homogenized brain tissue does not work because the brain homogenate suppresses antigen-specific lymphocyte proliferation. We now report a method that substantially reduces the suppressive activity. We used this non-suppressive brain homogenate to stimulate leukocytes from multiple sclerosis patients and controls. We also stimulated with common viruses for comparison. We measured proliferation, selected the responding CD3+ cells with flow cytometry, and sequenced their transcriptomes for mRNA and T-cell receptor sequences. The mRNA expression suggested that the brain-responding cells from MS patients are potentially pathogenic. The T-cell receptor repertoire of the brain-responding cells was clonal with minimal overlap with virus antigens.

Keywords

Adolescent, Adult, Autoantigens, Brain, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cell Proliferation, Female, Flow Cytometry, Humans, Lymphocyte Activation, Male, Multiple Sclerosis, Phenotype, Receptors, Antigen, T-Cell, Young Adult, multiple sclerosis, autoimmunity, autoantigen, T lymphocytes, T-cell receptor

DOI

10.3389/fimmu.2022.835763

PMID

35173742

PMCID

PMC8841344

PubMedCentral® Posted Date

1-31-2022

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes