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

Matsuoka, Eiji; Takenouchi, Norihiro; Hashimoto, Ken; Kashio, Nobuyuki; Moritoyo, Takashi; Higuchi, Itsuro; Isashiki, Yasushi; Satô, Eiichi; Osame, Mitsuhiro; Izumo, Shuji

doi:10.1007/s004010050903

Cited by 65 publications

(42 citation statements)

References 29 publications

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“…This distinguishing feature is observed in both peripheral blood and CSF of patients with HAM/TSP (9,10). Histopathological studies indicate the existence of HTLV-Iinfected cells as well as a local inflammatory response in the spinal cord lesions of HAM/TSP patients (11,12). It is therefore believed that the immune response to HTLV-I likely contributes to the inflammatory process of the CNS lesions in HAM/TSP patients and causes the clinical symptoms of HAM/TSP.…”

Section: Discussionmentioning

confidence: 95%

Cerebrospinal Fluid Neopterin, but not Osteopontin, is a Valuable Biomarker for the Treatment Response in Patients with HTLV-I-associated Myelopathy

et al. 2013

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Objective The concentrations of neopterin and osteopontin in the cerebrospinal fluid (CSF) were measured in patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in order to evaluate their utility as biomarkers for the treatment response. Methods Seven HAM/TSP patients were treated intravenously with high-dose methylprednisolone (1,000 mg/day) for 3 days. CSF samples were collected before and after the treatment. The neopterin and osteopontin concentrations were determined using high-performance liquid chromatography (HPLC) and an enzyme immunoassay, respectively. The clinical symptoms were evaluated using the Osame Motor Disability Score and the Urinary Disturbance Score. Results Four out of the seven patients showed an improvement in motor function with the treatment, and were therefore classed as responders. The pre-treatment CSF neopterin concentration exceeded the upper limit of normal in all seven of the patients, and tended to be higher in treatment responders as compared to non-responders. The CSF neopterin concentration was reduced following treatment in all patients. The mean CSF neopterin concentration significantly (p<0.01) decreased following treatment by almost 60% (from 124.1±79.9 nmol/L to 49.2±29.8 nmol/L). The mean CSF osteopontin concentration was significantly (p< 0.01) higher in the HAM/TSP patients in comparison to the 18 HTLV-1-seronegative patients who were designated as controls (9.54±4.53 mg/L vs. 3.72±3.04 mg/L). No significant (p=0.47) reduction of the CSF osteopontin concentration was observed following the intravenous administration of high-dose methylprednisolone. Conclusion These results indicate that the CSF neopterin concentration, but not the osteopontin concentration, is a potentially valuable biomarker for monitoring the treatment response in HAM/TSP patients. Furthermore, high pre-treatment CSF neopterin concentrations may be a predictive biomarker for a response to intravenous high-dose methylprednisolone therapy.

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Section: Discussionmentioning

confidence: 95%

Cerebrospinal Fluid Neopterin, but not Osteopontin, is a Valuable Biomarker for the Treatment Response in Patients with HTLV-I-associated Myelopathy

et al. 2013

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“…First, HTLV-1 might itself infect neurons or other resident cells in the central nervous system, and these infected cells could then be attacked by the HTLV-1-specific immune response. This possibility appears to be excluded by the observation that there is little or no HTLV-1 infection of resident cells in the central nervous system in HAM/TSP (Lehky et al, 1995;Matsuoka et al, 1998). Similarly, in HTLV-1-associated polymyositis, the provirus is present in invading CD4 þ T cells, not in macrophages or myocytes (Higuchi et al, 1996).…”

Section: Pathogenesis Of Ham/tsp and Other Htlv-1-associated Inflammamentioning

confidence: 93%

Cellular immune response to HTLV-1

2005

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There is strong evidence at the individual level and the population level that an efficient cytotoxic T lymphocyte (CTL) response to HTLV-1 limits the proviral load and the risk of associated inflammatory diseases such as HAM/TSP. This evidence comes from host population genetics, viral genetics, DNA expression microarrays and assays of lymphocyte function. However, until now there has been no satisfactory and rigorous means to define or to measure the efficiency of an antiviral CTL response. Recently, methods have been developed to quantify lymphocyte turnover rates in vivo and the efficiency of anti-HTLV-1 CTLs ex vivo. Data from these new techniques appear to substantiate the conclusion that variation between individual hosts in the rate at which a single CTL kills HTLV-1-infected lymphocytes is an important determinant, perhaps the decisive determinant, of the proviral load and the risk of HAM/ TSP. With these experimental data, it is becoming possible to refine, parameterize and test mathematical models of the immune control of HTLV-1, which are a necessary part of an understanding of this complex dynamic system.

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“…It is likely that CD4 ϩ cells play an important part in bystander damage in the central nervous system, because these are the predominant cells early in the active lesions of HAM͞TSP (52). Moreover, it is now clear that HTLV-I in the inflammatory lesions is present only in the invading CD4 ϩ cells (53,54). In this case, class II genes, which determine the antigen specificity of CD4 ϩ cells, could be associated with susceptibility to HAM͞TSP.…”

Section: Discussionmentioning

confidence: 99%

HLA alleles determine human T-lymphotropic virus-I (HTLV-I) proviral load and the risk of HTLV-I-associated myelopathy

Jeffery

Usuku

Hall

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

392

365

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The risk of disease associated with persistent virus infections such as HIV-I, hepatitis B and C, and human T-lymphotropic virus-I (HTLV-I) is strongly determined by the virus load. However, it is not known whether a persistent class I HLA-restricted antiviral cytotoxic T lymphocyte (CTL) response reduces viral load and is therefore beneficial or causes tissue damage and contributes to disease pathogenesis. HTLV-I-associated myelopathy (HAM͞TSP) patients have a high virus load compared with asymptomatic HTLV-I carriers. We hypothesized that HLA alleles control HTLV-I provirus load and thus inf luence susceptibility to HAM͞TSP. Here we show that, after infection with HTLV-I, the class I allele HLA-A*02 halves the odds of HAM͞TSP (P < 0.0001), preventing 28% of potential cases of HAM͞TSP. Furthermore, HLA-A*02 ؉ healthy HTLV-I carriers have a proviral load one-third that (P ‫؍‬ 0.014) of HLA-A*02 ؊ HTLV-I carriers. An association of HLA-DRB1*0101 with disease susceptibility also was identified, which doubled the odds of HAM͞TSP in the absence of the protective effect of HLA-A*02. These data have implications for other persistent virus infections in which virus load is associated with prognosis and imply that an efficient antiviral CTL response can reduce virus load and so prevent disease in persistent virus infections.

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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

Cited by 65 publications

References 29 publications

Cerebrospinal Fluid Neopterin, but not Osteopontin, is a Valuable Biomarker for the Treatment Response in Patients with HTLV-I-associated Myelopathy

Cerebrospinal Fluid Neopterin, but not Osteopontin, is a Valuable Biomarker for the Treatment Response in Patients with HTLV-I-associated Myelopathy

Cellular immune response to HTLV-1

HLA alleles determine human T-lymphotropic virus-I (HTLV-I) proviral load and the risk of HTLV-I-associated myelopathy

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