T cell recognition of self-antigen presenting cells by protein transfer assay reveals a high frequency of anti-myelin T cells in multiple sclerosis.
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 CD62(low) 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.
Bahbouhi
Bouchaib
B
INSERM, UMR 643, Nantes F44093, France.
Pettré
Ségolène
S
Berthelot
Laureline
L
Garcia
Alexandra
A
Elong Ngono
Annie
A
Degauque
Nicolas
N
Michel
Laure
L
Wiertlewski
Sandrine
S
Lefrère
Fabienne
F
Meyniel
Claire
C
Delcroix
Catherine
C
Brouard
Sophie
S
Laplaud
David-Axel
DA
Soulillou
Jean-Paul
JP
D000328:Adult; D000938:Antigen-Presenting Cells / Q000276:immunology*; D015703:Antigens, CD / Q000378:metabolism; D001323:Autoantibodies / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D005805:Genes, MHC Class I; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D009103:Multiple Sclerosis / Q000276:immunology* / Q000378:metabolism; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000276:immunology / Q000378:metabolism; D004676:Myelin Basic Protein; D009186:Myelin Sheath / Q000276:immunology* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000276:immunology / Q000378:metabolism; D012720:Severity of Illness Index; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
D015703:Antigens, CD; D001323:Autoantibodies; C499048:MBP protein, human; D004676:Myelin Basic Protein; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; D007371:Interferon-gamma