T cell receptor BV gene rearrangements in the spinal cords and cerebrospinal fluid of patients with amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal disorder whose etiology and pathogenesis remain unknown. Recent studies, however, have demonstrated the presence of inflammatory infiltrates within ALS spinal cord and suggested the possibility of an immune-mediated process in motor neuron degeneration. We have analyzed the diversity of T-cells in the spinal cord in ALS. Rever se transcriptase polymerase chain reaction (RT-PCR) with variable (V) regio n sequence specific oligonucleotide primers was used to amplify T-cell rece ptor (TCR)BV transcripts from spinal cords obtained at autopsy from patient s with ALS, patients who died without inflammatory disease of the central n ervous system, brains from patients with ALS, and brains from patients who died with inflammatory CNS disease. Sequencing was then performed on the am plified transcripts. An overall increase in the level of TCRBV 2 transcript s was detected in ALS specimens when compared to controls. This result was independent of the HLA genotype of the individual. Furthermore, enrichment of TCRBV2-positive T cells could be demonstrated in cerebrospinal fluid der ived from patients with ALS, using PCR analysis and a T cell stimulation as say with toxic shock syndrome toxin-l (TSST-1), a V beta 2-specific superan tigen. Our results suggest that an immunological process involving the spec ific expansion of V beta 2 TCR-positive T-cells may be important in the pat hogenesis of ALS. (C) 1999 Academic Press.