Common T-cell receptor V beta usage in oligoclonal T lymphocytes derived from cerebrospinal fluid and blood of patients with multiple sclerosis.
T-cell populations were investigated in the blood and cerebrospinal fluid of patients with multiple sclerosis and other neurological diseases. Individual T cells were directly cloned from the cerebrospinal fluid and blood before in vitro expansion, and their clonotypes were compared by Southern blot analysis of the rearrangement patterns of their T-cell receptor beta chain and gamma chain genes. This allowed the determination of whether two T cell clones shared the same T-cell receptor and thus arose from identical, clonally expanded (oligoclonal) progenitor T cells. As an extension of previous studies, oligoclonal T-cell clones were identified in both cerebrospinal fluid and blood populations in 5 of 9 patients with inflammatory demyelinating disease among a total of 486 blood and cerebrospinal fluid T-cell clones. In contrast, no clonally expanded T-cell populations were found among a total of 424 clones derived from either blood of 4 normal control subjects or blood and cerebrospinal fluid of 8 patients with other neurological diseases. Analysis of T-cell receptor V beta genes among 4 oligoclonal T-cell populations derived from 3 patients with multiple sclerosis demonstrated common usage of the V beta 12 gene segment. These data suggest that oligoclonal T cells share similar specificities and that clonal expansion may have resulted from specific stimulation by an antigen. Moreover, identical clones between blood and cerebrospinal fluid were observed in 3 of 9 patients with demyelinating disease, thus providing further evidence of an equilibrium between peripheral and central nervous system immune compartments.
Lee
S J
SJ
Department of Medicine, Brigham and Women's Hospital, Boston, MA.
Wucherpfennig
K W
KW
Brod
S A
SA
Benjamin
D
D
Weiner
H L
HL
Hafler
D A
DA
D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D015139:Blotting, Southern; D002675:Child, Preschool; D002999:Clone Cells; D015342:DNA Probes; D005260:Female; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor / Q000235:genetics*; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000097:blood / Q000134:cerebrospinal fluid / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D013601:T-Lymphocytes
D015342:DNA Probes