T cell recognition of self-antigen presenting cells by protein transfer assay reveals a high frequency of anti-myelin T cells in multiple sclerosis

• Published in: Brain (London, England : 1878) Vol. 133; no. 6; pp. 1622 - 1636
• Main Authors: Bahbouhi, Bouchaib, Pettré, Ségolène, Berthelot, Laureline, Garcia, Alexandra, Elong Ngono, Annie, Degauque, Nicolas, Michel, Laure, Wiertlewski, Sandrine, Lefrère, Fabienne, Meyniel, Claire, Delcroix, Catherine, Brouard, Sophie, Laplaud, David-Axel, Soulillou, Jean-Paul
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01-06-2010
• Subjects: Adult; Antigen-Presenting Cells - immunology; Antigens, CD - metabolism; Autoantibodies - metabolism; Biological and medical sciences; Cohort Studies; Female; Genes, MHC Class I; Humans; Immunologic Memory; Interferon-gamma - metabolism; Male; Medical sciences; Middle Aged; monocytes; Monocytes - immunology; Monocytes - metabolism; multiple sclerosis; Multiple Sclerosis - immunology; Multiple Sclerosis - metabolism; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Multiple Sclerosis, Relapsing-Remitting - immunology; Multiple Sclerosis, Relapsing-Remitting - metabolism; myelin; Myelin Basic Protein; Myelin Sheath - immunology; Myelin Sheath - metabolism; Nerve Tissue Proteins - immunology; Nerve Tissue Proteins - metabolism; Neurology; Severity of Illness Index; T-Lymphocyte Subsets - immunology; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Time Factors; Transcription Factors - immunology; Transcription Factors - metabolism; TRAP; trogocytosis; Young Adult; trogocytosis; monocytes; Nervous system diseases; Multiple sclerosis; Monocyte; Myelin; Central nervous system disease; T-Lymphocyte; Trap; High frequency; Protein; Inflammatory disease
• ISSN: 0006-8950; 1460-2156
• DOI: 10.1093/brain/awq074

Although peripheral blood myelin-autoreactive T cells are thought to play a key role in multiple sclerosis, they are generally considered to have qualitative differences rather than quantitative ones when compared to those found in healthy individuals. Here, we revisited the assessment of myelin-autoreactive T cells in a new approach based on their combined ability to acquire membrane proteins from autologous antigen presenting cells, and to respond to whole myelin extract as the stimulating autoantigen. Using this approach, the myelin-autoreactive T cell frequency in patients with multiple sclerosis was found to be unexpectedly high (n = 22, subtracted values median 2.08%, range 0–6%; background median 1%, range 0–4%) and to exceed that of age/gender-matched healthy individuals significantly (n = 18, subtracted values median 0.1%, range 0–5.3%, P < 0.0001; background median 1.45%, range 0.1–4%). Higher anti-myelin autoreactivity was stable in patients with multiple sclerosis after several months. These data correlated with whole myelin-induced gamma interferon-enzyme-linked immunosorbent spot assay performed under the same conditions, although the values obtained with enzyme-linked immunosorbent spot assay under all conditions were 58 times lower than with this new method. The myelin-autoreactive T cells were memory T cells expressing CD40L with a CD62low phenotype, suggesting their ability for homing to tissues. Collectively, these new data show a higher frequency of autoreactive T cells during multiple sclerosis than in age/gender-matched healthy individuals, and support an autoimmune aetiology in multiple sclerosis.