Increased HTLV-I proviral load and preferential expansion of HTLV-I tax-specific CD8+ T cells in cerebrospinal fluid from patients with HAM/TSP

• Published in: Annals of neurology 2001-12, Vol.50 (6), p.807-812
• Main Authors: Nagai, Masahiro, Yamano, Yoshihisa, Brennan, Meghan B., Mora, Carlos A., Jacobson, Steven
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Biological and medical sciences; Biomarkers; CD8-Positive T-Lymphocytes - virology; Cerebrospinal Fluid - cytology; Cerebrospinal Fluid - virology; Female; Flow Cytometry; Gene Products, tax - metabolism; Human T-lymphotropic virus 1 - physiology; Human viral diseases; Humans; Infectious diseases; Male; Medical sciences; Middle Aged; Paraparesis, Tropical Spastic - cerebrospinal fluid; Paraparesis, Tropical Spastic - immunology; Paraparesis, Tropical Spastic - virology; Peptide Fragments - metabolism; Viral diseases; Viral diseases of the nervous system; Viral Load
• ISSN: 0364-5134; 1531-8249
• DOI: 10.1002/ana.10065

To date, high human T‐cell lymphotropic virus type I proviral load in patients with human T‐cell lymphotropic virus type I‐associated myelopathy/tropical spastic paraparesis has been reported and is thought to be related to the pathogenesis of human T‐cell lymphotropic virus type I‐associated myelopathy/tropical spastic paraparesis. However, the proviral load in cerebrospinal fluid has not been well investigated. We measured human T‐cell lymphotropic virus type I proviral load in cerebrospinal fluid cells from human T‐cell lymphotropic virus type I‐associated myelopathy/tropical spastic paraparesis patients using real‐time quantitative polymerase chain reaction (TaqMan). Human T‐cell lymphotropic virus type I proviral load in cerebrospinal fluid cells were significantly higher than that of the matched peripheral blood mononuclear cells, and a high ratio of human T‐cell lymphotropic virus type I proviral load in cerebrospinal fluid cells to peripheral blood mononuclear cells were observed in patients with short duration of illness. Human T‐cell lymphotropic virus type I Tax‐specific CD8+ T cells, as detected by peptide‐loaded HLA tetramers, accumulated in cerebrospinal fluid compared with that in peripheral blood mononuclear cells, while the frequency of cytomegalovirus‐specific CD8+ T cells in cerebrospinal fluid was reduced. These observations suggest that accumulation of both human T‐cell lymphotropic virus type I‐infected cells and preferential expansion of human T‐cell lymphotropic virus type I‐specific CD8+ cells in cerebrospinal fluid may play a role in the pathogenesis of human T‐cell lymphotropic virus type I‐associated myelopathy/tropical spastic paraparesis.