Clinical pathophysiology of human T-lymphotropic virus-type 1-associated myelopathy/tropical spastic paraparesis

Frontiers in Microbiology

Volumn 3, Issue NOV, 2012, Pages

  Yamano, Yoshihisa ^a   Sato, Tomoo ^a  

^a ST MARIANNA UNIVERSITY SCHOOL OF MEDICINE   (Japan)

Author keywords

Diagnosis; Epidemiology; HAM TSP; HTLV 1; Pathogenesis; Prognosis; Retrovirus; Treatment

Indexed keywords

EID: 84876477600     PISSN: None     EISSN: 1664302X     Source Type: Journal    
DOI: 10.3389/fmicb.2012.00389     Document Type: Article

References (92)

1. Akahata, Y., Abrams, A., Johnson, K. R., Maloney, E. M., and Jacobson, S. (2012). Quantitative differences in HTLV-I antibody responses: classification and relative risk assessment for asymptomatic carriers and ATL and HAM/TSP patients from Jamaica. Blood 119, 2829-2836.
2. Alcindor, E., Valderrama, R., Canavaggio, M., Lee, H., Katz, A., Montesinos, C., et al. (1992). Imaging of human T-lymphotropic virus type I-associated chronic progressive myeloneuropathies. Neuroradiology 35, 69-74.
3. Araújo, A. Q., Alfonso, C. R., Schor, D., Leite, A. C., and de Andrada-Serpa,M. J. (1993). Clinical and demographic features of HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) in Rio de Janeiro, Brazil. Acta Neurol. Scand. 88, 59-62.
4. Araújo, A. Q, Andrade-Filho, A. S., Castro-Costa, C. M., Menna-Barreto, M., and Almeida, S. M. (1998). HTLV-I-associated myelopathy/tropical spastic paraparesis in Brazil: a nationwide survey. J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. 19, 536-541.
5. Arimura, K., Nakagawa, M., Izumo, S., Usuku, K., Itoyama, Y., Kira, J., et al. (2007). Safety and efficacy of interferon-α in 167 patients with human T-cell lymphotropic virus type 1-associated myelopathy. J. Neurovirol. 13, 364-372.
6. Azakami, K., Sato, T., Araya, N., Utsunomiya, A., Kubota, R., Suzuki, K.,et al. (2009). Severe loss of invariant NKT cells exhibiting anti-HTLV- 1 activity in patients with HTLV- 1-associated disorders. Blood 114, 3208-3215.
7. Bagnato, F., Butman, J. A., Mora, C. A., Gupta, S., Yamano, Y., Tasciyan, T. A., et al. (2005). Conventional magnetic resonance imaging features in patients with tropical spastic paraparesis. J. Neurovirol. 11, 525-534.
8. Bhigjee, A. I., Kelbe, C., Haribhai, H. C., Windsor, I. M., Hoffmann, M. H., Modi, G., et al. (1990). Myelopathy associated with human T cell lymphotropic virus type I (HTLV-I) in Natal, South Africa. A clinical and investigative study in 24 patients. Brain 113, 1307-1320.
9. Blattner, W. A., and Gallo, R. C. (1985). Epidemiology of human retroviruses. Leuk. Res. 9, 697-698.
10. Borden, E. C., Sen, G. C., Uze, G., Silverman, R. H., Ransohoff, R. M., Foster, G. R., et al. (2007). Interferons at age 50: past, current and future impact on biomedicine. Nat. Rev. Drug Discov. 6, 975-990.
11. Cavrois, M., Leclercq, I., Gout, O., Gessain, A., Wain-Hobson, S., and Wattel, E. (1998). Persistent oligoclonal expansion of human T-cell leukemia virus type 1-infected circulating cells in patients with tropical spastic paraparesis/HTLV-1 associated myelopathy. Oncogene 17, 77-82.
12. Croda, M. G.,de Oliveira,A. C.,Vergara, M. P., Bonasser, F., Smid, J., Duarte, A. J., et al. (2008). Corticosteroid therapy in TSP/HAM patients: the results from a 10 years open cohort. J. Neurol. Sci. 269, 133-137.
13. De Castro-Costa, C. M., Araújo, A. Q., Barreto, M. M., Takayanagui, O. M., Sohler, M. P., da Silva, E. L., et al. (2006). Proposal for diagnostic criteria of tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM). AIDS Res. Hum. Retroviruses 22, 931-935.
14. de Thé, G., and Bomford, R. (1993). An HTLV-I vaccine: why, how, for whom? AIDS Res. Hum. Retroviruses 9, 381-386.
15. de Thé, G., Gessain, A., and Gazzolo, L. (1985). Comparative seroepidemiology of HTLV-I and HTLV-III in the French West Indies and some African countries. Cancer Res. 45, 4633s-4636s.
16. Eguchi, K., Matsuoka, N., Ida, H., Nakashima, M., Sakai, M., Sakito, S., et al. (1992). Primary Sjogren's syndrome with antibodies to HTLV-I: clinical and laboratory features. Ann. Rheum. Dis. 51, 769-776.
17. Furuya, T., Nakamura, T., Fujimoto, T., Nakane, S., Kambara, C., Shirabe, S., et al. (1999). Elevated levels of interleukin-12 and interferongamma in patients with human T lymphotropic virus type Iassociated myelopathy. J. Neuroimmunol. 95, 185-189.
18. Furuya, T., Nakamura, T., Shirabe, S., Nishiura, Y., Tsujino, A., Goto, H., et al. (1997). Heightened transmigrating activity of CD4-positive T cells through reconstituted basement membrane in patients with human T-lymphotropic virus type I-associated myelopathy. Proc. Assoc. Am. Physicians 109, 228-236.
19. Gessain, A., and de Thé, G. (1996). Geographic and molecular epidemiology of primate T lymphotropic retroviruses: HTLV-I, HTLV-II, STLV-I, STLV-PP, and PTLV-L. Adv. Virus Res. 47, 377-426.
20. Gotuzzo, E., Cabrera, J., Deza, L., Verdonck, K., Vandamme, A. M., Cairampoma, R., et al. (2004). Clinical characteristics of patients in Peru with human T cell lymphotropic virus type 1-associated tropical spastic paraparesis. Clin. Infect. Dis. 39, 939-944.
21. Hanon, E., Goon, P., Taylor, G. P., Hasegawa, H., Tanaka, Y., Weber, J. N., et al. (2001). High production of interferon γ but not interleukin-2 by human T-lymphotropic virus type Iinfected peripheral blood mononuclear cells. Blood 98, 721-726.
22. Harrington, W. J. Jr., Sheremata, W. A., Snodgrass, S. R., Emerson, S., Phillips, S., and Berger, J. R. (1991). Tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM): treatment with an anabolic steroid danazol. AIDS Res. Hum. Retroviruses 7, 1031-1034.
23. Hinuma, Y., Nagata, K., and Hanaoka, M. (1981). Adult T-cell leukemia: antigen in an ATL cell line and detection of antibodies to the antigen in human sera. Proc. Natl. Acad. Sci. U.S.A. 78, 6476-6480.
24. Ijichi, S., Izumo, S., Eiraku, N., Machigashira, K., Kubota, R., Nagai, M., et al. (1993). An autoaggressive process against bystander tissues in HTLV-I- infected individuals: a possible pathomechanism of HAM/TSP. Med. Hypotheses 41, 542-547.
25. Ishida, T., Iida, S., Akatsuka, Y., Ishii, T., Miyazaki, M., Komatsu, H., et al. (2004). The CC chemokine receptor 4 as a novel specific molecular target for immunotherapy in adult T-cell leukemia/lymphoma. Clin. Cancer Res. 10, 7529-7539.
26. Ishida, T., Joh, T., Uike, N., Yamamoto, K., Utsunomiya, A., Yoshida, S., et al. (2012). Defucosylated anti- CCR4 monoclonal antibody (KW- 0761) for relapsed adult T-cell leukemia-lymphoma: a multicenter phase II study. J. Clin. Oncol. 30, 837-842.
27. Ishihara, S., Okayama, A., Stuver, S., Horinouchi, H., Shioiri, S., Murai, K., et al. (1994). Association of HTLV-I antibody profile of asymptomatic carriers with proviral DNA levels of peripheral blood mononuclear cells. J. Acquir. Immune Defic. Syndr. 7, 199-203.
28. Iwasaki, Y. (1990). Pathology of chronic myelopathy associated with HTLV-I infection (HAM/TSP). J. Neurol. Sci. 96, 103-123.
29. Izumo,S.,Goto,I.,Itoyama,Y.,Okajima, T., Watanabe, S., Kuroda, Y., et al. (1996). Interferon-alpha is effective in HTLV-I-associated myelopathy: a multicenter, randomized, doubleblind, controlled trial. Neurology 46, 1016-1021.
30. Izumo, S., Umehara, F., and Osame, M. (2000). HTLV-I-associated myelopathy. Neuropathology 20, S65-S68.
31. Jacobson, S., Shida, H., McFarlin, D. E., Fauci, A. S., and Koenig, S. (1990). Circulating CD8+ cytotoxic T lymphocytes specific for HTLV-I pX in patients with HTLV-I associated neurological disease. Nature 348, 245-248.
32. Kambara, C., Nakamura, T., Furuya, T., Nishiura, Y., Kawakami, A., Ichinose,K.,et al. (2002). Increased sialyl Lewis X antigen positive cells mediated by HTLV-1 infection in peripheral blood CD4+ T lymphocytes in patients with HTLV-1-associated myelopathy. J. Neuroimmunol. 125, 179-184.
33. Kamihira, S., Nakasima, S., Oyakawa, Y., Moriuti, Y., Ichimaru, M., Okuda, H., et al. (1987). Transmission of human T cell lymphotropic virus type I by blood transfusion before and after mass screening of sera from seropositive donors. Vox Sang. 52, 43-44.
34. Kaplan, J. E., Osame, M., Kubota, H., Igata, A., Nishitani, H., Maeda, Y., et al. (1990). The risk of development of HTLV-I-associated myelopathy/tropical spastic paraparesis among persons infected with HTLV-I. J. Acquir. Immune Defic. Syndr. 3, 1096-1101.
35. Kira, J., Fujihara, K., Itoyama, Y., Goto, I., and Hasuo, K. (1991). Leukoencephalopathy in HTLV-I-associated myelopathy/tropical spastic paraparesis: MRI analysis and a two year follow-up study after corticosteroid therapy. J. Neurol. Sci. 106, 41-49.
36. Krämer, A., Maloney, E. M., Morgan, O. S., Rodgers-Johnson, P., Manns, A., Murphy, E. L., et al. (1995). Risk factors and cofactors for human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in Jamaica. Am. J. Epidemiol. 142, 1212-1220.
37. Kubota, R., Soldan, S. S., Martin, R., and Jacobson, S. (2002). Selected cytotoxic T lymphocytes with high specificity for HTLV-I in cerebrospinal fluid from a HAM/TSP patient. J. Neurovirol. 8, 53-57.
38. Kuroda, Y., Matsui, M., Yukitake, M., Kurohara, K., Takashima, H., Takashima, Y., et al. (1995). Assessment of MRI criteria for MS in Japanese MS and HAM/TSP. Neurology 45, 30-33.
39. Lezin, A., Olindo, S., Oliere, S., Varrin-Doyer, M., Marlin, R., Cabre, P., et al. (2005). Human T lymphotropic virus type I (HTLV-I) proviral load in cerebrospinal fluid: a new criterion for the diagnosis of HTLV-I-associated myelopathy/tropical spastic paraparesis? J. Infect. Dis. 191, 1830-1834.
40. Lima, M. A., Harab, R. C., Schor, D., Andrada-Serpa, M. J., and Araújo, A. Q. (2007). Subacute progression of human T-lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis. J. Neurovirol. 13, 468-473.
41. Macchi, B., Balestrieri, E., Ascolani, A., Hilburn, S., Martin, F., Mastino, A., et al. (2011). Susceptibility of primary HTLV-1 isolates from patients with HTLV-1-associated myelopathy to reverse transcriptase inhibitors. Viruses 3, 469-483.
42. Maloney, E. M., Cleghorn, F. R., Morgan, O. S., Rodgers-Johnson, P., Cranston, B., Jack, N., et al. (1998). Incidence of HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in Jamaica and Trinidad. J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. 17, 167-170.
43. Martin, F., Castro, H., Gabriel, C., Adonis, A., Fedina, A., Harrison, L., et al. (2012). Ciclosporin a proof of concept study in patients with active, progressive HTLV-1 associated myelopathy/tropical spastic paraparesis. PLoS Negl. Trop. Dis. 6, e1675. doi:10.1371/journal.pntd.0001675
44. Martin, F., Fedina, A., Youshya, S., and Taylor, G. P. (2010). A 15- year prospective longitudinal study of disease progression in patients with HTLV-1 associated myelopathy in the UK. J. Neurol. Neurosurg. Psychiatr. 81, 1336-1340.
45. Matsuoka, E., Takenouchi, N., Hashimoto, K., Kashio, N., Moritoyo, T., Higuchi, I., et al. (1998). Perivascular T cells are infected with HTLV-I in the spinal cord lesions with HTLV-I-associated myelopathy/tropical spastic paraparesis: double staining of immunohisto- chemistry and polymerase chain reaction in situ hybridization. Acta Neuropathol. 96, 340-346.
46. Matsuzaki, T., Nakagawa, M., Nagai, M., Usuku, K., Higuchi, I., Arimura, K., et al. (2001). HTLV-I proviral load correlates with progression of motor disability in HAM/TSP: analysis of 239 HAM/TSP patients including 64 patients followed up for 10 years. J. Neurovirol. 7, 228-234.
47. Milagres, A. C., Jorge, M. L., Marchiori, P. E., and Segurado, A. A. (2002). Human T cell lymphotropic virus type 1-associated myelopathy in Sao Paulo, Brazil. Epidemiologic and clinical features of a university hospital cohort. Neuroepidemiology 21, 153-158.
48. Mochizuki, M. (1992). Uveitis associated with human T-cell lymphotropic virus type I. Am. J. Ophthalmol. 114, 123-129.
49. Moore, G. R., Traugott, U., Scheinberg, L. C., and Raine, C. S. (1989). Tropical spastic paraparesis: a model of virus-induced, cytotoxic T-cellmediated demyelination? Ann. Neurol. 26, 523-530.
50. Moreno-Carvalho, O. A., Nascimento-Carvalho, C. M. C., and Galvão-Castro, B. (1995). HTLV-I associated tropical spastic paraparesis. Cerebral spinal fluid evolutive aspects in 128 cases. Arq. Neuropsiquiatr. 53, 604-607.
51. Morgan, O. S., Rodgers-Johnson, P., Mora, C., and Char, G. (1989). HTLV-1 and polymyositis in Jamaica. Lancet 2, 1184-1187.
52. Nagai, M., Usuku, K., Matsumoto, W., Kodama, D., Takenouchi, N., Moritoyo, T., et al. (1998). Analysis of HTLV-I proviral load in 202 HAM/TSP patients and 243 asymptomatic HTLV-I carriers: high proviral load strongly predisposes to HAM/TSP. J. Neurovirol. 4, 586-593.
53. Nagai, M., Yamano, Y., Brennan, M. B., Mora, C. A., and Jacobson, S. (2001). Increased HTLV-I proviral load and preferential expansion of HTLV-I Tax-specific CD8+ T cells in cerebrospinal fluid from patients with HAM/TSP. Ann. Neurol. 50, 807-812.
54. Nakagawa, M., Izumo, S., Ijichi, S., Kubota, H., Arimura, K., Kawabata, M., et al. (1995). HTLV-I-associated myelopathy: analysis of 213 patients based on clinical features and laboratory findings. J. Neurovirol. 1, 50-61.
55. Nakagawa, M., Nakahara, K., Maruyama, Y., Kawabata, M., Higuchi, I., Kubota, H., et al. (1996). Therapeutic trials in 200 patients with HTLV-I-associated myelopathy/tropical spastic paraparesis. J. Neurovirol. 2, 345-355.
56. Ndhlovu, L. C., Snyder-Cappione, J. E., Carvalho, K. I., Leal, F. E., Loo, C. P., Bruno, F. R., et al. (2009). Lower numbers of circulating natural killer T (NK T) cells in individuals with human T lymphotropic virus type 1 (HTLV-1) associated neurological disease. Clin. Exp. Immunol. 158, 294-299.
57. Nishioka, K., Maruyama, I., Sato, K., Kitajima, I., Nakajima, Y., and Osame, M. (1989). Chronic inflammatory arthropathy associated with HTLV-I. Lancet 1, 441.
58. Oh,U.,Yamano,Y.,Mora,C.A.,Ohayon, J., Bagnato, F., Butman, J. A., et al. (2005). Interferon-β1a therapy in human T-lymphotropic virus type Iassociated neurologic disease. Ann. Neurol. 57, 526-534.
59. Olindo, S., Cabre, P., Lézin, A., Merle, H., Saint-Vil, M., Signate, A., et al. (2006). Natural history of human T-lymphotropic virus 1-associated myelopathy: a 14-year follow-up study. Arch. Neurol. 63, 1560-1566.
60. Olindo, S., Lézin, A., Cabre, P., Merle, H., Saint-Vil, M., Edimonana Kaptue, M., et al. (2005). HTLV- 1 proviral load in peripheral blood mononuclear cells quantified in 100 HAM/TSP patients: a marker of disease progression. J. Neurol. Sci. 237, 53-59.
61. Orland, J. R., Engstrom, J., Fridey, J., Sacher, R. A., Smith, J. W., Nass, C., et al. (2003). Prevalence and clinical features of HTLV neurologic disease in the HTLV outcomes study. Neurology 61, 1588-1594.
62. Osame, M. (2002). Pathological mechanisms of human T-cell lymphotropic virus type I-associated myelopathy (HAM/TSP). J. Neurovirol. 8, 359-364.
63. Osame, M., Janssen, R., Kubota, H., Nishitani, H., Igata, A., Nagataki, S., et al. (1990a). Nationwide survey of HTLV-I-associated myelopathy in Japan: association with blood transfusion. Ann. Neurol. 28, 50-56.
64. Osame, M., Igata, A., Matsumoto, M., Kohka, M., Usuku, K., and Izumo, S. (1990b). HTLV-I-associated myelopathy (HAM) treatment trials, retrospective survey and clinical and laboratory findings. Hematol. Rev. 3, 271-284.
65. Osame, M., Usuku, K., Izumo, S., Ijichi, N., Amitani, H., Igata, A., et al. (1986a). HTLV-I associated myelopathy, a new clinical entity. Lancet 1, 1031-1032.
66. Osame, M., Izumo, S., Igata, A., Matsumoto, M., Matsumoto, T., Sonoda, S., et al. (1986b). Blood transfusion and HTLV-I associated myelopathy. Lancet 2, 104-105.
67. Poiesz,B. J.,Ruscetti,F. W.,Gazdar,A. F., Bunn, P. A., Minna, J. D., and Gallo, R. C. (1980). Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma. Proc. Natl. Acad. Sci. U.S.A. 77, 7415-7419.
68. Puccioni-Sohler, M., Yamano, Y., Rios, M., Carvalho, S. M., Vasconcelos, C. C., Papais-Alvarenga, R., et al. (2007). Differentiationof HAM/TSP from patients with multiple sclerosis infected with HTLV-I. Neurology 68, 206-213.
69. Saito, M., Nakagawa, M., Kaseda, S., Matsuzaki, T., Jonosono, M., Eiraku, N., et al. (2004). Decreased human T lymphotropic virus type I (HTLV-I) provirus load and alteration in t cell phenotype after interferon-α therapy for HTLV-I-associated myelopathy/tropical spastic paraparesis. J. Infect. Dis. 189, 29-40.
70. Shirabe, S., Nakamura, T., Tsujino, A., Nishiura, Y., Furuya, T., Goto, H., et al. (1997). Successful application of pentoxifylline in the treatment of HTLV-I associated myelopathy. J. Neurol. Sci. 151, 97-101.
71. Sugiyama, H., Doi, H., Yamaguchi, K., Tsuji, Y., Miyamoto, T., and Hino, S. (1986). Significance of postnatal mother-to-child transmission of human T-lymphotropic virus type-I on the development of adult T-cell leukemia/lymphoma. J. Med. Virol. 20, 253-260.
72. Tajima, K., Kamura, S., Ito, S., Ito, M., Nagatomo, M., Kinoshita, K., et al. (1987). Epidemiological features of HTLV-I carriers, and incidence of ATL in an ATL-endemic island: a report of the community-based cooperative study in Tsushima, Japan. Int. J. Cancer 40, 741-746.
73. Takenouchi, N., Yamano, Y., Usuku, K., Osame, M., and Izumo, S. (2003). Usefulness of proviral load measurement for monitoring of disease activity in individual patients with human T-lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis. J. Neurovirol. 9, 29-35.
74. Tamiya, S., Matsuoka, M., Takemoto, S., Shimizu, K., Yamaguchi, K., Mita, S., et al. (1995). Adult T cell leukemia following HTLV- I-associated myelopathy/tropical spastic paraparesis: case reports and implication to the natural course of ATL. Leukemia 9, 1768-1770.
75. Tattermusch, S., Skinner, J. A., Chaussabel, D., Banchereau, J., Berry, M. P., McNab, F. W., et al. (2012). Systems biology approaches reveal a specific interferon-inducible signature in HTLV-1 associated myelopathy. PLoS Pathog. 8, e1002480. doi:10.1371/journal.ppat.1002480
76. Taylor, G. P., Goon, P., Furukawa, Y., Green, H., Barfield, A., Mosley, A., et al. (2006). Zidovudine plus lamivudine in human T-lymphotropic virus type-l-associated myelopathy: a randomised trial. Retrovirology 3, 63.
77. Tosswill, J. H., Taylor, G. P., Tedder, R. S., and Mortimer, P. P. (2000). HTLV-I/II associated disease in England and Wales, 1993-7: retrospective review of serology requests. BMJ 320, 611-612.
78. Uchiyama, T., Yodoi, J., Sagawa, K., Takatsuki, K., and Uchino, H. (1977). Adult T-cell leukemia: clinical and hematologic features of 16 cases. Blood 50, 481-492.
79. Umehara, F., Izumo, S., Nakagawa, M., Ronquillo, A. T., Takahashi, K., Matsumuro, K., et al. (1993). Immunocytochemical analysis of the cellular infiltrate in the spinal cord lesions in HTLV-I-associated myelopathy. J. Neuropathol. Exp. Neurol. 52, 424-430.
80. Umehara, F., Izumo, S., Ronquillo, A. T., Matsumuro, K., Sato, E., and Osame, M. (1994). Cytokine expression in the spinal cord lesions in HTLV-I-associated myelopathy. J. Neuropathol. Exp. Neurol. 53, 72-77.
81. Umehara, F., Nose, H., Saito, M., Fukuda, M., Ogino, M., Toyota, T., et al. (2007). Abnormalities of spinal magnetic resonance images implicate clinical variability in human T-cell lymphotropic virus type Iassociated myelopathy. J. Neurovirol. 13, 260-267.
82. Verdonck, K., González, E.,Van Dooren, S., Vandamme, A. M., Vanham, G., and Gotuzzo, E. (2007). Human Tlymphotropic virus 1: recent knowledge about an ancient infection. Lancet Infect. Dis. 7, 266-281.
83. Vernant, J. C., Maurs, L., Gessain, A., Barin, F., Gout, O., Delaporte, J. M., et al. (1987). Endemic tropical spastic paraparesis associated with human T-lymphotropic virus type I: a clinical and seroepidemiological study of 25 cases. Ann. Neurol. 21, 123-130.
84. Wattel, E., Vartanian, J. P., Pannetier, C., and Wain-Hobson, S. (1995). Clonal expansion of human T-cell leukemia virus type Iinfected cells in asymptomatic and symptomatic carriers without malignancy. J. Virol. 69, 2863-2868.
85. World Health Organization (WHO). (1989). Human T lymphotropic virus type 1, HTLV-1. Wkly. Epidemiol. Rec. 64, 382-383.
86. Yamamoto, K., Utsunomiya, A., Tobinai, K., Tsukasaki, K., Uike, N., Uozumi, K., et al. (2010). Phase I study of KW-0761, a defucosylated humanized anti-CCR4 antibody, in relapsed patients with adult T-cell leukemia-lymphoma and peripheral T-cell lymphoma. J. Clin. Oncol. 28, 1591-1598.
87. + T cells in a retrovirus-associated neuroinflammatory disorder. PLoS ONE 4, e6517. doi:10.1371/journal.pone.0006517
88. Yamano, Y., Nagai, M., Brennan, M., Mora, C. A., Soldan, S. S., Tomaru, U., et al. (2002). Correlation of human T-cell lymphotropic virus type 1 (HTLV-1) mRNA with proviral DNA load, virus-specific CD8 T cells, and disease severity in HTLV-1- associated myelopathy (HAM/TSP). Blood 99, 88-94.
89. Yamasaki, K., Kira, J., Koyanagi, Y., Kawano, Y., Miyano-Kurosaki, N., Nakamura, M., et al. (1997). Long term, high dose interferon-alpha treatment in HTLV-I-associated myelopathy/tropical spastic paraparesis: a combined clinical, virological and immunological study. J. Neurol. Sci. 147, 135-144.
90. Yoshie, O., Fujisawa, R., Nakayama, T., Harasawa, H., Tago, H., Izawa, D., et al. (2002). Frequent expression of CCR4 in adult T-cell leukemia and human T-cell leukemia virus type 1-transformed T cells. Blood 99, 1505-1511.
91. Yoshioka, A., Hirose, G., Ueda, Y., Nishimura, Y., and Sakai, K. (1993). Neuropathological studies of the spinal cord in early stage HTLV- I-associated myelopathy (HAM). J. Neurol. Neurosurg. Psychiatr. 56, 1004-1007.
92. Yu, F., Itoyama, Y., Fujihara, K., and Goto, I. (1991). Natural killer (NK) cells in HTLV-I- associated myelopathy/tropical spastic paraparesis-decrease in NK cell subset populations and activity in HTLV-I seropositive individuals. J. Neuroimmunol. 33, 121-128.