RESTRICTED T-CELL RECEPTOR DELTA-CHAIN GENES REPERTOIRE IN PERIPHERAL-BLOOD OF MULTIPLE-SCLEROSIS PATIENTS

Multiple sclerosis (MS) is a chronic inflammatory disease characterize d by focal demyelination of central nervous system (CNS), Susceptibili ty 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 alpha/beta T lymphocytes also gamma/delta T cells may have autoreactive potential, TCR delta repertoire in peripheral blood of M S patients has been studied, TCR delta repertoire, as assessed by V de lta-J delta rearrangements, has been analysed in 13 MS cases and in 30 healthy individuals by seminested PCR technique, Oligonucleotide prim ers specific for six V delta regions and for J delta 1 gene were used for amplification of V delta-J delta junctional region responsible for the diversity of gamma/delta TCR. In the majority of MS patients PAGE analysis of V delta 1-J delta 1, V delta 3-J delta 1 and V delta 5-J delta 1 rearrangements showed single-band or two-band pattern. The mos t striking result has been observed in V delta 5-J delta 1 rearrangeme nt, where in nine cases studied single band and in four patients two b ands have been found, In all but one MS cases multi-band pattern of V delta 2-J delta 1 rearrangement was obtained, None of the 13 MS patien ts showed single-band rearrangement pattern of V delta 4-J delta 1 and V delta 6-J delta 1. Contrary to the MS group almost all healthy indi viduals produced smear-like or multi-band pattern of V delta 1-V delta 5 to J delta 1 rearrangements. On the basis of the banding pattern pr oduced by V delta-J delta rearrangement in MS, it can be suggested tha t T lymphocytes had undergone clonal expansion in vivo, most likely du e to stimulation by antigen related to CNS. In particular a very consi stent single-band pattern of V delta 5-J delta 1 rearrangement observe d in almost all MS patients studied, argues very strongly for a signif icant role of gamma/delta T cells with V delta 5 rearrangement in the pathogenesis of MS. However, it cannot be excluded that the observed p atterns of TCR delta gene rearrangement in MS patients may represent s econdary changes to CNS damage.