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ABSTRACT: Pulmonary involvement has been identified in human T-lymphotropic virus type I (HTLV-I) carriers and patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). However, the relationship between HTLV-I infection and lung disease is poorly understood. The occurrence of HTLV-I-specific immune responses in the lungs of patients infected with HTLV-I with pulmonary involvement was investigated. The frequency of HTLV-I-specific CD8+ cells and the amount of HTLV-I proviral DNA were determined in bronchoalveolar lavage fluid cells and peripheral blood mononuclear cells (PBMCs) from five patients with HAM/TSP and one HTLV-I carrier who had pulmonary involvement. HTLV-I-specific CD8+ cells were detected by flow cytometry using human leukocyte antigen/antigen complex multimers. The analysis of bronchoalveolar lavage fluid revealed lymphocytosis in five of six patients. HTLV-I provirus was detected in the bronchoalveolar lavage fluid cells of all patients, and the proviral load in these cells was comparable to that in PBMCs. The frequency of HTLV-I-specific CD8+ cells in the bronchoalveolar lavage fluid cells was 5.1 times higher than that in PBMCs. Immunohistochemically, clusters formed by HTLV-I-specific CD8+ cells were detected in lung tissue by in situ tetramer staining. No samples were available from patients infected with HTLV-I without lung disorders. Whether accumulation of CD8+ cells is specific to patients with pulmonary involvement remains unclear. These results indicate that HTLV-I-specific CD8+ cells accumulate and HTLV-I-infected cells exist in the lungs of patients infected with HTLV-I with pulmonary involvement.
Journal of Medical Virology 07/2012; 84(7):1120-7. · 2.82 Impact Factor
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ABSTRACT: Human T-lymphotropic virus-1 (HTLV-1) causes HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukemia-lymphoma in individuals with dysfunctional immune responses. In this study, to characterize the HTLV-1-specific cytotoxic T lymphocyte (CTL) populations in asymptomatic HTLV-1 carriers (ACs), HAM/TSP patients, and carriers with autoimmune disorders (CAIDs), we examined the role of programmed death-1 and its ligand (PD-1/PD-L1) in HTLV-1-specific CTL functions using an HTLV-1 Tax/HLA-A*0201 tetramer and an HTLV-1 Tax/HLA-A*2402 tetramer. Interestingly, the percentage of HTLV-1 Tax301-309/HLA-A*2402 tetramer(+)CD8(+) cells expressing PD-1 in ACs was significantly higher than the percentage of HTLV-1 Tax11-19/HLA-A*0201 tetramer(+)CD8(+) cells expressing PD-1. PD-1 expression was significantly downregulated on HTLV-1-specific CTLs in HAM/TSP compared with ACs. PD-L1 expression was observed in a small proportion of unstimulated lymphocytes from ACs and was greater in ACs than in HAM/TSP and CAIDs after short-term culture. Furthermore, CTL degranulation was impaired in HAM/TSP, whereas anti-PD-L1 blockade significantly increased CTL function in ACs. Downregulation of PD-1 on HTLV-1-specific CTLs and loss of PD-L1 expression in HAM/TSP and CAIDs, along with impaired function of HTLV-1-specific CTLs in HAM/TSP, may underlie the apparently dysfunctional immune response against HTLV-1.
Human immunology 08/2011; 72(11):1001-6. · 2.55 Impact Factor
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ABSTRACT: T cell immunoglobulin and mucin domain-containing molecule-3 (Tim-3) and programmed cell death-1 (PD-1) are T cell exhaustion molecules. We investigated the expression of Tim-3 and PD-1 in human T-lymphotropic virus type I (HTLV-I) infection. Tim-3 expression, but not PD-1 expression, was reduced on CD4(+) and CD8(+) T cells of HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients and HTLV-I carriers as compared with healthy controls. Tim-3 expression was also reduced in HTLV-I Tax-specific cytotoxic T lymphocytes (CTLs) as compared with cytomegalovirus-specific CTLs. Tim-3(+), but not PD-1(+), Tax-specific CTLs produced less interferon-γ and exhibited low cytolytic activity. However, we observed no difference in the expression of Tim-3 or cytolytic activity between Tax-specific CTLs of HAM/TSP patients or carriers. Moreover, HTLV-I-infected CD4(+) T cells showed decreased Tim-3 expression. These data suggest that Tim-3 expression is reduced in HTLV-I infection and that a high number of Tim-3(-) HTLV-I-specific CTLs preserves their cytolytic activity, thereby controlling viral replication.
The Journal of Infectious Diseases 04/2011; 203(7):948-59. · 6.41 Impact Factor
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Tomohiro Kozako,
Masaki Akimoto,
Shingo Toji,
Yohann White,
Susumu Suzuki,
Takehiro Arima,
Yukio Suruga,
Kakushi Matsushita,
Hiroshi Shimeno,
Shinji Soeda, Ryuji Kubota,
Shuji Izumo,
Kimiharu Uozumi,
Naomichi Arima
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ABSTRACT: Human T-cell lymphotropic virus type I (HTLV-1) causes adult T-cell leukemia/lymphoma and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The different patterns of clinical diseases are thought to be linked to immunogenetic host factors. A variety of autoimmune diseases, such as Sjögren's syndrome, have been reported in persons infected with HTLV-1, although the precise relationship between these disorders and HTLV-1 infection remains unknown. There is no report on the repertoire of HTLV-1-specific CD8+ T-cells in HAM/TSP patients or carriers with autoimmune diseases, both characterized by an abnormal immune state. In this study, to characterize HTLV-1-specific CD8+ T-cells in asymptomatic HTLV-1 carriers, HAM/TSP patients and carriers with autoimmune diseases, we examined the frequency and diversity of HTLV-1-specific CD8+ T-cells using HTLV-1 tetramers. HTLV-1 Env-specific CD8+ T-cells were significantly more frequent in HAM/TSP and carriers with autoimmune diseases compared with asymptomatic HTLV-1 carriers, while the frequency of HTLV-1 Tax-specific CD8+ T-cells was not significantly different among them. CD8+ cells binding to HTLV-1 Tax tetramers in carriers with autoimmune diseases were significantly reduced compared with HAM/TSP patients. This study demonstrates the importance of CD8+ T-cells recognizing HTLV-1 Env-tetramers in HAM/TSP patients and carriers with autoimmune diseases, thereby suggesting that the diversity, frequency and repertoire of HTLV-1 Env-specific CD8+ T-cell clones may be related to the hyperimmune response in HAM/TSP and carriers with autoimmune diseases, although different immunological mechanisms may mediate the hyperimmunity in these conditions.
Journal of Medical Virology 03/2011; 83(3):501-9. · 2.82 Impact Factor
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Shimeru Kamihira,
Yoshihisa Yamano,
Masako Iwanaga,
Daisuke Sasaki,
Masahiro Satake,
Akihiko Okayama,
Kazumi Umeki, Ryuji Kubota,
Shuji Izumo,
Kazunari Yamaguchi,
Toshiki Watanabe
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ABSTRACT: Human T-cell leukemia virus type-1 (HTLV-1) proviral load (VL) is an important determinant of viral pathogenesis and malignant evolution. Although VL has been quantified by in-house real-time quantifiable polymerase chain reaction (qPCR) technology, little is known about the harmonization among different VL assay systems. We evaluated intra- and inter-laboratory variability of VL measured at six laboratories using the same DNA samples seropositive for HTLV-1 in a two-step manner. The first study measured 60 samples by original in-house assays, finding that the median intra- and inter-laboratory coefficient of variation (CV) was 44.9% (range, 25.4-71.8%) and 59.9% (34.2-93.4%), respectively. The inter-laboratory correlation coefficients ranged from 0.760 to 0.875, indicating that VL were measured with good precision in each laboratory, but inter-laboratory regression slopes differed from 0.399 to 2.206, indicating that VL were measured with a wide variation between laboratories. To examine the effect of standardization of reference materials (RM) on the VL variability, we performed a second study using only 20 samples by substituting RM for plasmid including the HTLV-1 pX region. The median inter-laboratory CV for raw pX copy number was reduced significantly from 66.9% to 35.7%, whereas the median CV for the internal control remained almost unchanged, resulting in no improvement in inter-laboratory CV for VL. This indicates that each in-house assay system worked well with good precision, but standardizing RM alone was insufficient for harmonization. The relevant choice of not only RM, but also internal control genes for data normalization is expected to be realistic to standardize HTLV-1 VL measurement.
Cancer Science 11/2010; 101(11):2361-7. · 3.33 Impact Factor
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Kazuko Azakami,
Tomoo Sato,
Natsumi Araya,
Atae Utsunomiya, Ryuji Kubota,
Kenshi Suzuki,
Daisuke Hasegawa,
Toshihiko Izumi,
Hidetoshi Fujita,
Satoko Aratani,
Ryoji Fujii,
Naoko Yagishita,
Hajime Kamijuku,
Takuro Kanekura,
Ken-ichiro Seino,
Kusuki Nishioka,
Toshihiro Nakajima,
Yoshihisa Yamano
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ABSTRACT: Invariant natural killer T (iNKT) cells are unique T cells that regulate the immune response to microbes, cancers, and autoimmunity. We assessed the characteristics of iNKT cells from persons infected with human T-lymphotropic virus type 1 (HTLV-1). Whereas most infected persons remain asymptomatic carriers (ACs) throughout their lives, a small proportion, usually with high equilibrium proviral loads,develop 2 diseases: HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukemia (ATL). We demonstrated that the frequency of iNKT, NK, and dendritic cells in the peripheral blood of HAM/TSP and ATL patients is decreased. We also observed an inverse correlation between the iNKT cell frequency and the HTLV-1 proviral load in the peripheral blood of infected persons. Notably, in vitro stimulation of peripheral blood cells with alpha-galactosylceramide led to an increase in the iNKT cell number and a subsequent decrease in the HTLV-1-infected T-cell number in samples from ACs but not HAM/TSP or ATL patients. Our results suggest that iNKT cells contribute to the immune defense against HTLV-1, and iNKT-cell depletion plays an important role in the pathogenesis of HAM/TSP and ATL. Therefore, iNKT cell-based immunotherapy may be an effective strategy for preventing these HTLV-1-associated disorders.
Blood 09/2009; 114(15):3208-15. · 9.90 Impact Factor
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ABSTRACT: As the pathogenesis of AIDS dementia complex (ADC), cytokines such as TNF-alpha and IL-1beta have been thought to have toxic effects on CNS cells and induce neuronal cell death. However, many of the discussions have been based on the studies done by in vitro experiments. There are only a few reports which demonstrate proinflammatory cytokines directly in vivo in HIV encephalitis (HIVE) brains, and roles of these cytokines with relation to HIV-1 infection are not yet clarified. In the present study, we examined 11 autopsy cases of HIVE using immunohistochemistry, and explored which cell types expressed these cytokines and whether expression of cytokines was related to viral infection. IL-1beta was detected in the frontal white matter of all 11 cases where microglial nodules were observed to varying degrees, whereas TNF-alpha was detected in seven cases. IL-1beta- or TNF-alpha-positive cells were almost restricted to CD68-positive macrophages/microglia and mild expression of these cytokines by astrocytes was observed in two cases with severe HIVE. IL-1beta was detected in some HIVp24-positive multinucleated giant cells. However, we could not detect TNF-alpha expression in the HIVp24-positive cells, which indicates that IL-1beta is induced by HIV-1 infection. In conclusion, a macrophage/microglia lineage is the main cell type to release cytokines in HIVE, and IL-1beta expression by HIV-1-infected cells may be one of the important factors for induction of HIVE. In addition, many non-infected macrophages/microglia as well as some astrocytes express IL-1beta and TNF-alpha, which might contribute to pathogenesis of ADC.
Neuropathology 02/2009; 29(4):433-42. · 2.02 Impact Factor
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ABSTRACT: To determine the relationship between the human immunodeficiency virus type 1 (HIV-1) encephalitis (HIVE) and diffuse poliodystrophy in the acquired immunodeficiency syndrome dementia complex, we examined the neuropathologic features in brain autopsy tissue specimens of HIV-1-infected patients with (n = 11) or without HIVE (n = 9). The brains were free of opportunistic diseases and major cerebrovascular lesions. In both groups, there was diffuse microglial activation, astrocytic gliosis, and decreased excitatory amino acid transporter 2 (EAAT-2) immunoreactivity. These changes did not correlate either with the severity of encephalitis or local HIV-1 infection as detected by p24 immunostaining. Some activated microglia expressed EAAT-2; interleukin-1beta and tumor necrosis factor were detected only in microglial nodules of HIVE cases but not in areas with diffusely activated microglia. There was a significant negative correlation between the areas of EAAT-2 expression and numbers of activated microglia (p < 0.01) in cases with decreased EAAT-2. These data indicate that diffuse cortical changes may occur independently of HIVE in acquired immunodeficiency syndrome patients. The expression of EAAT-2 by activated microglia suggests that they might exert a compensatory effect that protects neurons from glutamate neurotoxicity.
Journal of Neuropathology and Experimental Neurology 01/2009; 68(2):199-209. · 4.26 Impact Factor
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ABSTRACT: Human T-lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a slowly progressive, inflammatory disease of the central nervous system (CNS). We report a patient with transverse myelitis, who exhibited acute onset and rapid progression of the disease and whose symptoms resembled those observed in multiple sclerosis with spinal cord presentation. During neurological exacerbation of the condition, the HTLV-I proviral load in the cerebrospinal fluid (CSF) increased to 10 times that in the peripheral blood. This suggests that the accumulation of HTLV-I-infected cells in the CNS contributes to neurological exacerbation. Based on the increased proviral load in the CSF, we diagnosed the disease as acute progressive HAM/TSP. The measurement of the HTLV-I proviral load in the CSF is useful for the diagnosis of HAM/TSP and for monitoring its progression.
Journal of NeuroVirology 12/2008; 14(5):459-63. · 2.31 Impact Factor
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ABSTRACT: Human T-lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients show high immune responses to HTLV-I. However, it is unclear whether the cytotoxic T lymphocyte (CTL) responses to other chronic viruses also increase. We investigated the responses in the peripheral blood by using HLA-A*0201/peptide pentamers. The frequency of cytomegalovirus (CMV)-specific CTL tended to be higher in HAM/TSP patients than in healthy controls (HCs). The frequency of CMV-specific CTL positively correlated with that of HTLV-I Tax-specific CTL. The frequency of Foxp3+ cells in CD4+ lymphocytes tended to be higher in HAM/TSP patients than in ACs and HCs. The expression level of Foxp3 was lower in HAM/TSP patients than in HCs and was inversely correlated with the CMV-specific CTL frequency. A percentage of Foxp3+ cells showed a positive correlation with the HTLV-I proviral load. These results suggest that a decrease in the Foxp3 expression may contribute to the high immune response to CMV and that the Foxp3+ regulatory T cells may play a role in the immune surveillance of HTLV-I.
Journal of Neuroimmunology 08/2008; 200(1-2):115-24. · 2.96 Impact Factor
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Eiji Matsuura,
Fujio Umehara,
Hirohisa Nose,
Itsuro Higuchi,
Eiji Matsuoka,
Koutarou Izumi, Ryuji Kubota,
Mineki Saito,
Shuji Izumo,
Kimiyoshi Arimura,
Mitsuhiro Osame
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ABSTRACT: The objective of this study was to investigate the association of human T-lymphotropic virus-type I (HTLV-I) infection with sporadic inclusion body myositis in 11 patients from an endemic area in Japan. The clinical features were consistent with sporadic inclusion body myositis, and anti-HTLV-I antibodies were present in the sera of all patients. Their muscle biopsies showed the diagnostic features of inclusion body myositis, including endomysial T-cell infiltration, rimmed vacuoles, deposits of phosphorylated tau, and abnormal filaments in the nuclei and cytoplasm of the myofibers. The fibers expressed major histocompatibility complex class I antigens and were invaded by CD8 and CD4 cells. In a single human leukocyte antigen-A2-positive patient, in situ human leukocyte antigen-A*0201 / Tax11-19-pentamer staining showed pentamer-positive cells surrounding the muscle fibers. Double-immunogold silver staining and polymerase chain reaction in situ hybridization revealed that HTLV-I proviral DNA was localized on helper-inducer T cells, but not on muscle fibers. Human T-lymphotropic virus-type I proviral loads in peripheral blood mononuclear cells from each patient were similar to those in HTLV-I-associated myelopathy/tropical spastic paraparesis. This study suggests that HTLV-I infection may be one of the causes of sporadic inclusion body myositis, as has been reported in human immunodeficiency virus type-1 infection.
Journal of Neuropathology and Experimental Neurology 02/2008; 67(1):41-9. · 4.26 Impact Factor
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Hirohisa Nose, Ryuji Kubota,
Nilufer P Seth,
Peter K Goon,
Yuetsu Tanaka,
Shuji Izumo,
Koichiro Usuku,
Yoshiro Ohara,
Kai W Wucherpfennig,
Charles R M Bangham,
Mitsuhiro Osame,
Mineki Saito
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ABSTRACT: HLA-DRB1*0101 is associated with susceptibility to human T lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Here, we used a synthetic tetramer of DRB1*0101 and its epitope peptide to analyze HTLV-1-specific CD4(+) T cells ex vivo. The frequency of tetramer(+)CD4(+) T cells was significantly greater in patients with HAM/TSP than in healthy HTLV-1 carriers (HCs) at a given proviral load and correlated with HTLV-1 tax messenger RNA expression in HCs but not in patients with HAM/TSP. These cells displayed an early to intermediate effector memory phenotype and were preferentially infected by HTLV-1. T cell receptor gene analyses of 2 unrelated DRB1*0101-positive patients with HAM/TSP showed similar Vbeta repertoires and amino acid motifs in complementarity-determining region 3. Our data suggest that efficient clonal expansion of virus-specific CD4(+) T cells in patients with HAM/TSP does not simply reflect higher viral burden but rather reflects a rapid turnover caused by preferential infection and/or in vivo stimulation by major histocompatibility complex-peptide complexes.
The Journal of Infectious Diseases 01/2008; 196(12):1761-72. · 6.41 Impact Factor
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British Journal of Haematology 10/2007; 138(5):666-7. · 4.94 Impact Factor
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ABSTRACT: Human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is an inflammatory neurological disease. Patients with HAM/TSP show high proviral load despite increased HTLV-I Tax-specific CTL. It is still unknown whether the CTL efficiently eliminate the virus in vivo and/or whether a naturally occurring variant virus becomes predominant by escaping from the CTL. To address these issues, we sequenced a large number of HTLV-I tax genes from HLA-A*02 HAM/TSP patients and estimated synonymous and nonsynonymous changes of the genes to detect positive selection pressure on the virus. We found the pressures in three of six CTL epitopes in HTLV-I Tax, where amino acid substitutions preferentially occurred. Although some of variant viruses were not recognized by the CTL, no variant viruses accumulated within 3-8 years, indicating genetic stability of HTLV-I tax gene. These results suggest that CTL eliminate the infected cells in vivo and naturally occurring variant viruses do not predominate. As Tax is a regulatory protein which controls viral replication, the amino acid substitutions in Tax may reduce viral fitness for replication. Viral fitness and host immune response may contribute to the viral evolution within the infected individuals. Furthermore, the genetic stability in the epitopes despite the antiviral pressures suggests that the three epitopes can be the candidate targets for HTLV-I vaccine development.
The Journal of Immunology 06/2007; 178(9):5966-72. · 5.79 Impact Factor
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Nō to shinkei = Brain and nerve 08/2006; 58(7):595-604.
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Hirohisa Nose,
Mineki Saito,
Koichiro Usuku,
Amir H Sabouri,
Toshio Matsuzaki, Ryuji Kubota,
Nobutaka Eiraku,
Yoshitaka Furukawa,
Shuji Izumo,
Kimiyoshi Arimura,
Mitsuhiro Osame
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ABSTRACT: The authors have previously developed a logistic regression equation to predict the odds that a human T-cell lymphotropic virus type 1 (HTLV-1)-infected individual of specified genotype, age, and provirus load has HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in southern Japan. This study evaluated whether this equation is useful predictor for monitoring asymptomatic HTLV-1-seropositive carriers (HCs) in the same population. The authors genotyped 181 HCs for each HAM/TSP-associated gene (tumor necrosis factor [TNF]-alpha-863A/C, stromal cell-derived factor 1 (SDF-1) +801G/A, human leukocyte antigen [HLA]-A*02, HLA-Cw*08, HTLV-1 tax subgroup) and measured HTLV-1 provirus load in peripheral blood mononuclear cells using real-time polymerase chain reaction (PCR). Finally, the odds of HAM/TSP for each subject were calculated by using the equation and compared the results with clinical symptoms and laboratory findings. Although no clear difference was seen between the odds of HAM/TSP and either sex, family history of HAM/TSP or adult T-cell lenkemia (ATL), history of blood transfusion, it was found that brisk patellar deep tendon reflexes, which suggest latent central nervous system compromise, and flower cell-like abnormal lymphocytes, which is the morphological characteristic of ATL cells, were associated with a higher odds of HAM/TSP. The best-fit logistic regression equation may be useful for detecting subclinical abnormalities in HCs in southern Japan.
Journal of NeuroVirology 07/2006; 12(3):171-7. · 2.31 Impact Factor
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Mineki Saito,
Masanori Nakagawa,
Shun Kaseda,
Toshio Matsuzaki,
Manabu Jonosono,
Nobutaka Eiraku, Ryuji Kubota,
Norihiro Takenouchi,
Masahiro Nagai,
Yoshitaka Furukawa,
Koichiro Usuku,
Shuji Izumo,
Mitsuhiro Osame
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ABSTRACT: To analyze the mechanism by which interferon (IFN)-alpha is effective against human T cell lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP), we investigated the T cell phenotype and HTLV-I provirus load in peripheral blood mononuclear cells from 25 patients with HAM/TSP that were obtained before and after administration of IFN-alpha. The frequency of memory (CD45RA(-)CD27(+)) T cells that were CD8(high+), CXCR3(+) cell populations, and HTLV-I provirus loads were significantly decreased after treatment. The proportion of memory T cells in the CD8(high+) cell population correlated well with HTLV-I provirus load, whereas the proportion of effector (CD45RA(+)CD27(-)) cells in the CD8(high+) cell population was inversely correlated with provirus load. Interestingly, the frequency of perforin expression in CD8(high+) cells was significantly decreased after treatment in patients who experienced clinical improvement, whereas patients who did not experience clinical improvement showed an increased frequency of perforin expression. Our data suggest that fluctuations in these cell subsets are associated with both the immunomodulatory effect of IFN-alpha and the observed clinical benefit of IFN-alpha treatment in patients with HAM/TSP.
The Journal of Infectious Diseases 02/2004; 189(1):29-40. · 6.41 Impact Factor
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Mitsuhiro Osame,
Koichiro Usuku,
Fujio Umehara,
Mineki Saito,
Yoshitaka Furukawa, Ryuji Kubota,
Masahiro Nagai,
Itsuro Higuchi,
Masanori Nakagawa,
Kimiyoshi Arimura,
Shuji Izumo
Nihon Naika Gakkai Zasshi 10/2003; 92(9):1673-82.
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ABSTRACT: Human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is an inflammatory neurologic disease caused by HTLV-1 infection, in which HTLV-1-infected CD4(+) T cells and HTLV-1-specific CD8(+) T cells may play a role in the disease pathogenesis. Patients with HAM/TSP have high proviral loads despite vigorous virus-specific CD8(+) T-cell responses; however, it is unknown whether the T cells are efficient in eliminating the virus in vivo. To define the dynamics of HTLV-1-specific CD8(+) T-cell responses, we investigated longitudinal alterations in HTLV-1 proviral load, amino acid changes in an immunodominant viral epitope, frequency of HTLV-1-specific T cells, and degeneracy of T-cell recognition in patients with HAM/TSP. We showed that the frequency and the degeneracy of the HTLV-1-specific CD8(+) T cells correlated well with proviral load in the longitudinal study. The proviral load was much higher in a patient with low degeneracy of HTLV-1-specific T cells compared to that in a patient with comparable frequency but higher degeneracy of the T cells. Furthermore, in a larger number of patients divided into 2 groups by the proviral load, those with high proviral load had lower degeneracy of T-cell recognition than those with low proviral load. Sequencing analysis revealed that epitope mutations were remarkably increased in a patient when the frequency and the degeneracy were at the lowest. These data suggest that HTLV-1-specific CD8(+) T cells with degenerate specificity are increased during viral replication and control the viral infection.
Blood 05/2003; 101(8):3074-81. · 9.90 Impact Factor
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ABSTRACT: Clinical and laboratory findings were examined for 111 human T-cell lymphotropic virus type I (HTLV-I)-infected blood donors. HTLV-I provirus loads in subjects with a family history of adult T-cell leukemia (ATL) or HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) tended to be higher than those in subjects without a family history of these conditions. There were 3 asymptomatic patients with ATL, 4 with a history of uveitis, 7 with hyperreflexia in the lower limbs, and 3 with urinary frequency in the night. The mean CD4 cell/CD8 cell ratio +/- SD was significantly lower (p<.0001) in subjects with hyperreflexia in the lower limbs (1.3 +/- 0.2) than in subjects without any clinical abnormalities (1.7 +/- 0.6), suggesting that subjects with hyperreflexia in the lower limbs already have some immunologic abnormalities. The concordance of HTLV-I infection between husband and wife was lower in this study than in a previous study. HTLV-I-related inflammatory symptoms were more frequent (p =.021, Fisher exact test; OR = 9.5; 95% CI, 1.7-53.5) in HTLV-I tax A-infected donors (3 [50%] of 6 donors) than in HTLV-I tax B-infected donors (10 [9.5%] of 105 donors), suggesting different risks of HTLV-I-related symptoms according to the virus genotype.
JAIDS Journal of Acquired Immune Deficiency Syndromes 03/2003; 32(3):328-34. · 4.43 Impact Factor
