Human T-lymphotropic virus type I-associated myelopathy and tax gene expression in CD4+ T lymphocytes.
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.
Moritoyo
T
T
Department of Microbiology, University of Minnesota, Minneapolis, 55455, USA.
Reinhart
T A
TA
Moritoyo
H
H
Sato
E
E
Izumo
S
S
Osame
M
M
Haase
A T
AT
D000328:Adult; D000368:Aged; D001483:Base Sequence; D001921:Brain / Q000473:pathology / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism* / Q000821:virology; D002478:Cells, Cultured; D046508:Culture Techniques; D005260:Female; D015870:Gene Expression; D016355:Genes, pX; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D015458:Leukemia, T-Cell / Q000235:genetics / Q000473:pathology / Q000821:virology; D008297:Male; D008969:Molecular Sequence Data; D015493:Paraparesis, Tropical Spastic / Q000235:genetics / Q000473:pathology / Q000821:virology*; D012333:RNA, Messenger / Q000032:analysis; D012367:RNA, Viral / Q000032:analysis; D013116:Spinal Cord / Q000473:pathology / Q000821:virology
D012333:RNA, Messenger; D012367:RNA, Viral