Human T-lymphotropic virus type I-associated myelopathy and tax gene expression in CD4+ T lymphocytes

Takashi Moritoyo, Todd A. Reinhart, Hiroyoko Moritoyo, Eiichi Sato, Shuji Izumo, Mitsuhiro Osame, Ashley T. Haase

Research output: Contribution to journalArticlepeer-review

101 Scopus citations

Abstract

Infection by human T-lymphotropic virus type I (HTLV-I) is associated with adult T-cell leukemia and a slowly progressive disease of the central nervous system (CNS), HTLV-I-associated myelopathy/tropical spastic paraparesis, characterized pathologically by inflammation and white matter degeneration in the spinal cord. One of the explanations for the 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 along with cytokines cause the pathological changes. Because both in the circulation and in the cerebrospinal fluid, CD8+ cytotoxic T lymphocytes are primarily reactive to the product of the HTLV-I tax gene, we sought evidence of expression of this gene within cells in the inflammatory lesions. After using double-label in situ hybridization techniques, we now report definitive localization of HTLV- I tax gene expression in CD4+ T lymphocytes in areas of inflammation and white matter destruction. These findings lend support to a hypothetical scheme of neuropathogenesis in which HTLV-I tax gene expression provokes and sustains an immunopathological process that progressively destroys myelin and axons in the spinal cord.

Original languageEnglish (US)
Pages (from-to)84-90
Number of pages7
JournalAnnals of Neurology
Volume40
Issue number1
DOIs
StatePublished - Jul 1 1996

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