T cell recognition of self-antigen presenting cells by protein transfer assay reveals a high frequency of anti-myelin T cells in multiple sclerosis
| Autor: | Sophie Brouard, Bouchaib Bahbouhi, Laure Michel, Jean-Paul Soulillou, Alexandra Garcia, Nicolas Degauque, Annie Elong Ngono, Fabienne Lefrère, Ségolène Pettré, Sandrine Wiertlewski, Laureline Berthelot, Catherine Delcroix, David-Axel Laplaud, Claire Meyniel |
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| Rok vydání: | 2010 |
| Předmět: |
Adult
Male Multiple Sclerosis Time Factors T-Lymphocytes T cell Antigen-Presenting Cells Genes MHC Class I Nerve Tissue Proteins Severity of Illness Index Monocytes Cohort Studies Interferon-gamma Young Adult Myelin Multiple Sclerosis Relapsing-Remitting Antigen Antigens CD T-Lymphocyte Subsets medicine Humans Antigen-presenting cell Myelin Sheath Autoantibodies CD40 biology Multiple sclerosis Myelin Basic Protein T lymphocyte Middle Aged medicine.disease Myelin basic protein medicine.anatomical_structure Immunology biology.protein Female Neurology (clinical) Immunologic Memory Transcription Factors |
| Zdroj: | Brain. 133:1622-1636 |
| ISSN: | 1460-2156 0006-8950 |
| DOI: | 10.1093/brain/awq074 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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