Clonal expansions of activated gamma/delta T cells in recent-onset multiple sclerosis.
Multiple sclerosis (MS) is a chronic disease characterized by focal demyelination of the white matter of the brain and spinal cord. Central nervous system damage appears to be mediated by infiltrating T lymphocytes and macrophages, and a central role for autoreactive CD4+ T cells has been proposed. However, the initial immune events that lead to the chronic process of MS remain unidentified. We now present evidence that a subset of T lymphocytes bearing gamma/delta T-cell antigen receptors has been activated in patients with recent-onset disease. Cells recovered from the cerebrospinal fluid of subjects with MS were cultured for short periods of time in medium supplemented with T-cell growth factors. Expansions of V delta 1 and V delta 2 T-cell receptor-bearing lymphocytes were found only in cell populations obtained from subjects with recent-onset disease. Similar populations were not expanded in subjects with chronic MS or other neurological diseases. Junctional region sequencing showed the expanded gamma/delta T cells to be oligoclonal in nature, suggestive of specific stimulation by antigen. These results reveal a fundamental difference in the immunopathogenesis of acute vs. chronic disease and provide additional insight into the autoimmune nature of MS.
Shimonkevitz
R
R
Rocky Mountain Multiple Sclerosis Center, Englewood, CO 80110.
Colburn
C
C
Burnham
J A
JA
Murray
R S
RS
Kotzin
B L
BL
D001483:Base Sequence; D002478:Cells, Cultured; D002555:Cerebrospinal Fluid / Q000166:cytology*; D006801:Humans; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000145:classification / Q000235:genetics / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000276:immunology*; D012689:Sequence Homology, Nucleic Acid; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors
D016692:Receptors, Antigen, T-Cell, gamma-delta