[Autoimmune mechanism in HAM/TSP].
Identification of the localization of HTLV-I proviral DNA in the central nervous system (CNS) is crucial to elucidate the pathogenesis of HTLV-I associated myelopathy (HAM)/Tropical spastic paraparesis (TSP). We have developed a new sensitive detection method, called two-step PCR in situ hybridization, which enabled us to detect the HTLV-I proviral DNA in paraffin embedded spinal cord tissue sections from HAM/TSP. HTLV-I proviral DNA was detected only in the nucleus of lymphocytes that infiltrated into the spinal cord. However, no proviral DNA was amplified in any neuronal cells, including neurons and glial cells. This indicates that the demyelination of the spinal cord by HTLV-I is unlikely as a result of viral infection of oligodendrocytes or neuronal cells. The sequence of T-cell receptor (TCR) V beta genes of the lymphocytes in the spinal cord lesions from the same HAM/TSP autopsy cases revealed an unique CDR3 motif, LCASSLXGG (one letter amino acid. X is any amino acid) which is identical to those found in mice encephalitogenic T-cell clones specific for myelin basic protein (MBP) peptide and two more motifs of LCASSPT (G), LCASSGRL were identical to those described in brain lesions of multiple sclerosis and in a rat T-cell clone from experimental allergic encephalomyeilitis (EAE) lesions, respectively. Taken together, the present results demonstrated that T-cells, which are reactive to the myelin component, such as MBP or PLP, may be activated by HTLV-I infection and infiltrate into the spinal cord lesions of HAM/TSP patients and suggested that an autoimmune mechanism may be involved in the pathogenesis of HAM/TSP.
Hara
H
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Department of Neurology, Faculty of Medicine, Kyushu University.
D000595:Amino Acid Sequence; D015551:Autoimmunity; D004279:DNA, Viral / Q000032:analysis; D006801:Humans; D008969:Molecular Sequence Data; D015493:Paraparesis, Tropical Spastic / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000032:analysis
D004279:DNA, Viral; D011948:Receptors, Antigen, T-Cell