HUMAN T-LYMPHOTROPIC VIRUS TYPE I-ASSOCIATED MYELOPATHY AND TAX GENE-EXPRESSION IN CD4(-LYMPHOCYTES() T)

Infection by human T-lymphotropic virus type I (HTLV-I) is associated with adult T-cell leukemia and a slowly progressive disease of the cen tral nervous system (CNS), HTLV-I-associated myelopathy/tropical spast ic paraparesis, characterized pathologically by inflammation and white matter degeneration in the spinal cord. One of the explanations for t he tissue destruction is that HTLV-I infects cells in the CNS, or HTLV -I-infected CD4(+) T lymphocytes enter the CNS, and this drives local expansion of virus-specific CD8(+) cytotoxic T lymphocytes, which alon g with cytokines cause the pathological changes. Because both in the c irculation and in the cerebrospinal fluid, CD8(+) cytotoxic T lymphocy tes are primarily reactive to the product of the HTLV-I tax gene, we s ought evidence of expression of this gene within cells in the inflamma tory lesions. After using double-label in situ hybridization technique s, we now report definitive localization of HTLV-I tax gene expression in CD4(+) T lymphocytes in areas of inflammation and white matter des truction. These findings lend support to a hypothetical scheme of neur opathogenesis in which HTLV-I tax gene expression provokes and sustain s an immunopathological process that progressively destroys myelin and axons in the spinal coed.