title: Double control systems for human T-cell leukemia virus type 1 by innate and acquired immunity.
abstract: Human T-cell leukemia virus type 1 (HTLV-1) is the causative retrovirus of adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-1-specific T-cell responses elicit antitumor and antiviral effects in experimental models, and are considered to be one of the most important determinants of the disease manifestation, since they are activated in HAM/TSP but not in ATL patients. The combination of low T-cell responses and elevated HTLV-1 proviral loads are features of ATL, and are also observed in a subpopulation of HTLV-1 carriers at the asymptomatic stage, suggesting that these features may be underlying risk factors. These risks may potentially be reduced by vaccination to activate HTLV-1-specific T-cell responses. HAM/TSP and ATL patients also differ in their levels of HTLV-1 mRNA expression, which are generally low in vivo but slightly higher in HAM/TSP patients. Our recent study indicated that viral expression in HTLV-1-infected T-cells is suppressed by stromal cells in culture through type-I IFNs. The suppression was reversible after isolation from the stromal cells, mimicking a long-standing puzzling phenomenon in HTLV-1 infection where the viral expression is very low in vivo and rapidly induced in vitro. Collectively, HTLV-1 is controlled by both acquired and innate immunity in vivo: HTLV-1-specific T-cells survey infected cells, and IFNs suppress viral expression. Both effects would contribute to a reduction in viral pathogenesis, although they may potentially influence or conflict with one another. The presence of double control systems for HTLV-1 infection provides a new concept for understanding the pathogenesis of HTLV-1-mediated malignant and inflammatory diseases.
authors.affiliation: Department of Immunotherapeutics, Tokyo Medical and Dental University, Graduate School, Tokyo, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Kannagi
authors.forename: Atsuhiko
authors.initials: A
authors.lastname: Hasegawa
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kinpara
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Shimizu
authors.forename: Ayako
authors.initials: A
authors.lastname: Takamori
authors.forename: Atae
authors.initials: A
authors.lastname: Utsunomiya
mesh_terms: D056704:Adaptive Immunity; D000328:Adult; D015490:HTLV-I Infections / Q000276:immunology* / Q000821:virology; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D006801:Humans; D016399:Lymphoma, T-Cell / Q000276:immunology* / Q000821:virology