Abstract
Multiple sclerosis (MS) is a chronic inflammatory disease characterized by focal demyelination of central nervous system (CNS). Susceptibility to MS is thought to be affected by multiple genes including HLA and T cell receptor (TCR) genes. In view of the recent evidence, that in addition to α/β T lymphocytes also γ/δ T cells may have autoreactive potential, TCR delta repertoire in peripheral blood of MS patients has been studied. TCR delta repertoire, as assessed by Vδ‐Jδ rearrangements, has been analysed in 13 MS cases and in 30 healthy individuals by seminested PCR technique. Oligonucleotide primers specific for six Vδ regions and for Jδ1 gene were used for amplification of Vδ‐Jδ junctional region responsible for the diversity of γ/δ TCR. In the majority of MS patients PAGE analysis of Vδ1‐Jδ1, Vδ3‐Jδ1 and Vδ5‐Jδ1 rearrangements showed single‐band or two‐band pattern. The most striking result has been observed in Vδ5‐Jδ1 rearrangement, where in nine cases studied single band and in four patients two bands have been found. In all but one MS cases multi‐band pattern of Vδ2‐Jδ1 rearrangement was obtained. None of the 13 MS patients showed single‐band rearrangement pattern of Vδ4‐Jδ1 and Vδ6‐Jδl. Contrary to the MS group almost all healthy individuals produced smear‐like or multi‐band pattern of Vδ1‐Vδ5 to Jδ1 rearrangements. On the basis of the banding pattern produced by Vδ‐Jδ rearrangement in MS, it can be suggested that T lymphocytes had undergone clonal expansion in vivo, most likely due to stimulation by antigen related to CNS. In particular a very consistent single‐band pattern of Vδ5‐Jδ1 rearrangement observed in almost all MS patients studied, argues very strongly for a significant role of γ/δ T cells with Vδ5 rearrangement in the pathogenesis of MS. However, it cannot be excluded that the observed patterns of TCR δ gene rearrangement in MS patients may represent secondary changes to CNS damage.
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