Multiple sclerosis: brain-infiltrating CD8+ T cells persist as clonal expansions in the cerebrospinal fluid and blood.
We surveyed the T cell receptor repertoire in three separate compartments (brain, cerebrospinal fluid, and blood) of two multiple sclerosis patients who initially had diagnostic brain biopsies to clarify their unusual clinical presentation but were subsequently confirmed to have typical multiple sclerosis. One of the brain biopsy specimens had been previously investigated by microdissection and single-cell PCR to determine the clonal composition of brain-infiltrating T cells at the single-cell level. Using complementarity-determining region 3 spectratyping, we identified several identical, expanded CD8+ (but not CD4+) T cell clones in all three compartments. Some of the expanded CD8+ T cells also occurred in sorted CD38+ blood cells, suggesting that they were activated. Strikingly, some of the brain-infiltrating CD8+ T cell clones persisted for >5 years in the cerebrospinal fluid and/or blood and may thus contribute to the progression of the disease.
Institute for Clinical Neuroimmunology, Ludwig-Maximilians University, 81377 Munich, Germany.
Christian
C
Skulina
Stephan
S
Schmidt
Klaus
K
Dornmair
Holger
H
Babbe
Axel
A
Roers
Klaus
K
Rajewsky
Hartmut
H
Wekerle
Reinhard
R
Hohlfeld
Norbert
N
Goebels
D000595:Amino Acid Sequence; D001483:Base Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002999:Clone Cells; D017931:DNA Primers; D006801:Humans; D007150:Immunohistochemistry; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000097:blood / Q000134:cerebrospinal fluid / Q000235:genetics / Q000276:immunology*; D016133:Polymerase Chain Reaction; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000235:genetics* / Q000276:immunology
D017931:DNA Primers; D017260:Receptor-CD3 Complex, Antigen, T-Cell