Human T-lymphotropic virus type 1 (HTLV-1)–associated myelopathy/tropical spastic paraparesis (HAM/TSP) is chronic myelopathy characterized by slowly progressive spastic paraparesis and urinary dysfunction. A few biomarkers in the cerebrospinal fluid are known to be related to disease activity, but no biomarker has been reported in peripheral blood. This study aims to explore the expression level of the adhesion molecule during the expression level of the adhesion molecule among HAM/TSP disease activity. In lymphocyte function–associated antigen 1 and DNAX accessory molecule 1, no variation in expression levels specific to HTLV-1 infection was observed in CD4-positive T cells; however, TSLC1 expression was higher in HAM patients than in asymptomatic carriers and non-infected persons. TSLC1 tended to be higher in patients whose symptoms were worsening. On the contrary, the expression level of TSLC1 in CD8-positive T cells was lower in HAM patients than in asymptomatic carriers, and this tendency was stronger in patients whose symptoms had deteriorated. No significant correlation was found between TSLC1 and either of the transcription factors Tax or HBZ in any T cell group. Therefore, TSLC1 expression in CD4-positive T cells might be a useful biomarker of HAM/TSP disease activity.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
Bangham CR, Osame M (2005) Cellular immune response to HTLV-1. Oncogene 24:6035–6046
Boles KS, Barchet W, Diacovo M, Cella M, Colonna M (2005) The tumor suppressor TSLC1/NECL-2 triggers NK-cell and CD8-positive T cell responses through the cell-surface receptor CRTAM. Blood 106:779–786
Dewan MZ, Takamatsu N, Hidaka T, Hatakeyama K, Nakahata S, Fujisawa J, Katano H, Yamamoto N, Morishita K (2008) Critical role for TSLC1 expression in the growth and organ infiltration of adult T cell leukemia cells in vivo. J Virol 82:11958–11963
Fujisawa J, Seiki M, Kiyokawa T, Yoshida M (1985) Functional activation of the long terminal repeat of human T cell leukemia virus type I by a trans-acting factor. Proc Natl Acad Sci U S A 82:2277–2281
Fukudome K, Furuse M, Fukuhara N, Orita S, Imai T, Takagi S, Nagira M, Hinuma Y, Yoshie O (1992) Strong induction of ICAM-1 in human T cells transformed by human T-cell-leukemia virus type 1 and depression of ICAM-1 or LFA-1 in adult T-cell-leukemia-derived cell lines. Int J Cancer 52:418–427
Gessain A, Barin F, Vernant JC, Gout O, Maurs L, Calender A, de The G (1985) Antibodies to human T-lymphotropic virus type-I in patients with tropical spastic paraparesis. Lancet 2:407–410
Hanon E, Stinchcombe JC, Saito M, Asquith BE, Taylor GP, Tanaka Y, Weber JN, Griffiths GM, Bangham CR (2000) Fratricide among CD8(+) T lymphocytes naturally infected with human T cell lymphotropic virus type I. Immunity 13:657–664
Ijichi S, Izumo S, Eiraku N, Machigashira K, Kubota R, Nagai M, Ikegami N, Kashio N, Umehara F, Maruyama I, Osame M (1993) An autoaggressive process against bystander tissues in HTLV-1-infected individuals: a possible pathomechanism of HAM/TSP. Med Hypotheses 41:542–547
Itoyama Y, Minato S, Kira J, Goto I, Sato H, Okochi K, Yamamoto N (1988) Spontaneous proliferation of peripheral blood lymphocytes increased in patients with HTLV-1-associated myelopathy. Neurology 38:1302–1307
Jacobson S (2002) Immunopathogenesis of human T cell lymphotropic virus type I-associated neurologic disease. J Infect Dis 186:S187–S192
Kim SJ, Nair A, Fernandez S, Mathes L, Lairmore MD (2006) Enhancement of LFA-1-mediated T cell adhesion by human T lymphotropic virus type 1 p12I1. J Immunol 176:5463–5470
Kinoshita T, Shimoyama M, Tobinai K, Ito M, Ito S, Ikeda S, Tajima K, Shimotohno K, Sugimura T (1989) Detection of mRNA for the tax1/rex1 gene of human T-cell leukemia virus type I in fresh peripheral blood mononuclear cells of adult T-cell leukemia patients and viral carriers by using the polymerase chain reaction. Proc Natl Acad Sci U S A 86:5620–5624
Kitze B, Usuku K, Izumo S, Nakamura M, Shiraki H, Ijichi S, Yashiki S, Fujiyoshi T, Sonoda S, Osame M (1996) Diversity of intrathecal antibody synthesis against HTLV-I and its relation to HTLV-I associated myelopathy. J Neurol 243:393–400
Kubota R, Umehara F, Izumo S, Ijichi S, Matsumuro K, Yashiki S, Fujiyoshi T, Sonoda S, Osame M (1994) HTLV-I proviral DNA amount correlates with infiltrating CD4-positive lymphocytes in the spinal cord from patients with HTLV-I-associated myelopathy. J Neuroimmunol 53:23–29
Makiyama J, Kobayashi S, Watanabe E, Ishigaki T, Kawamata T, Nakashima M, Yamagishi M, Nakano K, Tojo A, Watanabe T, Uchimaru K (2019) CD4+CADM1+ cell percentage predicts disease progression in HTLV-1 carriers and indolent adult T-cell leukemia/lymphoma. Cancer Sci 110:3746–3753
Matsuoka E, Takenouchi N, Hashimoto K, Kashio N, Moritoyo T, Higuchi I, Isashiki Y, Sato E, Osame M, Izumo S (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 immunohistochemistry and polymerase chain reaction in situ hybridization. Acta Neuropathol 96:340–346
Murakami Y (2005) Involvement of a cell adhesion molecule, TSLC1/IGSF4, in human oncogenesis. Cancer Sci 96:543–552
Nagai M, Kubota R, Greten TF, Schneck JP, Leist TP, Jacobson S (2001) Increased activated human T cell lymphotropic virus type I (HTLV-I) Tax11-19-specific memory and effector CD8-positive cells in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis: correlation with HTLV-1 provirus load. J Infect Dis 183:197–205
Nagasato K, Nakamura T, Ohishi K, Shibayama K, Motomura M, Ichinose K, Tsujihata M, Nagataki S (1991) Active production of anti-human T-lymphotropic virus type I (HTLV-I) IgM antibody in HTLV-I-associated myelopathy. J Neuroimmunol 32:105–109
Nakagawa M, Izumo S, Ijichi S, Kubota H, Arimura K, Kawabata M, Osame M (1995) HTLV-1-associated myelopathy: analysis of 213 patients based on clinical features and laboratory findings. J Neuro-Oncol 1:50–61
Nakagawa M, Nakahara K, Maruyama Y, Kawabata M, Higuchi I, Kubota H, Izumo S, Arimura K, Osame M (1996) Therapeutic trials in 200 patients with HTLV-I-associated myelopathy/tropical spastic paraparesis. J Neuro-Oncol 2:345–355
Nakahata S, Saito Y, Marutsuka K, Hidaka T, Maeda K, Hatakeyama K, Shiraga T, Goto A, Takamatsu N, Asada Y, Utsunomiya A, Okayama A, Kubuki Y, Shimoda K, Ukai Y, Kurosawa G, Morishita K (2012) Clinical significance of CADM1/TSLC1/IgSF4 expression in adult T-cell leukemia/lymphoma. Leukemia 26:1238–1246
Osame M (2002) Pathological mechanisms of human T-cell lymphotropic virus type I-associated myelopathy (HAM/TSP). J Neuro-Oncol 8:359–364
Osame M, Usuku K, Izumo S, Ijichi N, Amitani H, Igata A, Matsumoto M, Tara M (1986) HTLV-I associated myelopathy, a new clinical entity. Lancet 1:1031–1032
Richardson JH, Edwards AJ, Cruickshank JK, Rudge P, Dalgleish AG (1990) In vivo cellular tropism of human T-cell leukemia virus type 1. J Virol 64:5682–5687
Saito M (2010) Immunogenetics and the pathological mechanisms of human T-cell leukemia virus type 1- (HTLV-1-)associated myelopathy/tropical spastic paraparesis (HAM/TSP). Interdiscip Perspect Infect Dis https://doi.org/10.1155/2010/478461
Saito M, Nakagawa M, Kaseda S, Matsuzaki T, Jonosono M, Eiraku N, Kubota R, Takenouchi N, Nagai M, Furukawa Y, Usuku K, Izumo S, Osame M (2004) Decreased human T lymphotropic virus type I (HTLV-I) provirus load and alteration in T cell phenotype after interferon-alpha therapy for HTLV-I-associated myelopathy/tropical spastic paraparesis. J Infect Dis 189:29–40
Sasaki H, Nishikata I, Shiraga T, Akamatsu E, Fukami T, Hidaka T, Kubuki Y, Okayama A, Hamada K, Okabe H, Murakami Y, Tsubouchi H, Morishita K (2005) Overexpression of a cell adhesion molecule, TSLC1, as a possible molecular marker for acute-type adult T-cell leukemia. Blood 105:1204–1213
Seiki M, Hattori S, Hirayama Y, Yoshida M (1983) Human adult T-cell leukemia virus: complete nucleotide sequence of the provirus genome integrated in leukemia cell DNA. Proc Natl Acad Sci U S A 80:3618–3622
Shimoyama M, Minato K, Tobinai K, Nagai M, Setoya T, Takenaka T, Ishihara K, Watanabe S, Hoshino H, Miwa M, Kinoshita M, Okabe S, Fukushima N, Inada N (1983) Atypical adult T-cell leukemia-lymphoma: diverse clinical manifestations of adult T-cell leukemia-lymphoma. Jpn J Clin Oncol 13:165–187
Sodroski JG, Rosen CA, Heseltine WA (1984) Trans-acting transcriptional activation of the long terminal repeat of human T lymphotropic viruses in infected cells. Science 225:381–385
Umehara F, Nakamura A, Izumo S, Kubota R, Ijichi S, Kashino N, Hashimoto K, Usuku K, Sato E, Osame M (1994) Apoptosis of T lymphocytes in the spinal cord lesions in HTLV-I-associated myelopathy: a possible mechanism to control viral infection in the central nervous system. J Neuropathol Exp Neurol 53:617–624
Usuku K, Sonoda S, Osame M, Yashiki S, Takahashi K, Matsumoto M, Sawada T, Tsuji K, Tara M, Igata A (1988) HLA haplotype-linked high immune responsiveness against HTLV-1 in HTLV-1-associated myelopathy: comparison with adult T-cell leukemia/lymphoma. Ann Neural 23:S143–S150
Watanabe T (1997) HTLV-1-associated disease. Int J Hematol 66:257–278
Yamaguchi K, Nishimura H, Kohrogi H, Jono M, Miyamoto Y, Takatsuki K (1983) A proposal for smoldering adult T-cell leukemia: a clinicopathologic study of five cases. Blood 62:758–766
Yamano Y, Nagai M, Brennan M, Mora CA, Soldan SS, Tomaru U, Takenouchi N, Izumo S, Osame M, Jacobson S (2002) Correlation of human T-cell lymphotropic virus type 1 (HTLV-1) mRNA with proviral DNA load, virus-specific CD8-positive T cells, and disease severity in HTLV-1-associated myelopathy (HAM/TSP). Blood 99:88–94
Yamano Y, Takenouchi N, Li HC, Tomaru U, Yao K, Grant CW, Maric DA, Jacobson S (2005) Virus-induced dysfunction of CD4-positive CD25-positive T cells in patients with HTLV-I-associated neuroimmunological disease. J Clin Invest 115:1361–1368
Yasunaga J, Matsuoka M (2007) Leukaemogenic mechanism of human T-cell leukaemia virus type I. Rev Med Virol 17:301–311
We thank Enago (www.enago.jp) for the English language review.
This work was supported partly by KAKENHI Grant Number 245911280 from JSPS, and the Japan Agency for Medical Research and Development (AMED) (NT: 16ek0109026h0003, MT: 17fk0108111j0101). The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript.
The institutional review boards of the authors’ institutions approved this research and written informed consent was obtained from all study participants.
Conflict of interest
The authors declare that they have no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Takenouchi, N., Tanaka, M., Sato, T. et al. Expression of TSLC1 in patients with HAM/TSP. J. Neurovirol. 26, 404–414 (2020). https://doi.org/10.1007/s13365-020-00838-z
- Human T-lymphotropic virus type I (HTLV-I)
- HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP)
- Tumor suppressor in lung cancer-1 (TSLC1)
- Clinical symptoms