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Potential role of HTLV-1 Tax-specific cytotoxic t lymphocytes expressing a unique t-cell receptor to promote inflammation of the central nervous system in myelopathy associated with HTLV-1.
Tanaka, Yukie; Sato, Tomoo; Yagishita, Naoko; Yamauchi, Junji; Araya, Natsumi; Aratani, Satoko; Takahashi, Katsunori; Kunitomo, Yasuo; Nagasaka, Misako; Kanda, Yoshinobu; Uchimaru, Kaoru; Morio, Tomohiro; Yamano, Yoshihisa.
Afiliação
  • Tanaka Y; Department of Molecular Microbiology, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
  • Sato T; Research Core, Institute of Research, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
  • Yagishita N; Department of Rare Diseases Research, Institute of Medical Science, St. Marianna University School of Medicine, Kawasaki, Japan.
  • Yamauchi J; Division of Neurology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan.
  • Araya N; Department of Rare Diseases Research, Institute of Medical Science, St. Marianna University School of Medicine, Kawasaki, Japan.
  • Aratani S; Department of Rare Diseases Research, Institute of Medical Science, St. Marianna University School of Medicine, Kawasaki, Japan.
  • Takahashi K; Division of Neurology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan.
  • Kunitomo Y; Department of Rare Diseases Research, Institute of Medical Science, St. Marianna University School of Medicine, Kawasaki, Japan.
  • Nagasaka M; Department of Rare Diseases Research, Institute of Medical Science, St. Marianna University School of Medicine, Kawasaki, Japan.
  • Kanda Y; Advanced Business Promotion Department, Business Development Segment, LSI Medience Corporation, Tokyo, Japan.
  • Uchimaru K; Department of Rare Diseases Research, Institute of Medical Science, St. Marianna University School of Medicine, Kawasaki, Japan.
  • Morio T; Department of Rare Diseases Research, Institute of Medical Science, St. Marianna University School of Medicine, Kawasaki, Japan.
  • Yamano Y; Division of Neurology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan.
Front Immunol ; 13: 993025, 2022.
Article em En | MEDLINE | ID: mdl-36081501
Human T-lymphotropic virus 1 (HTLV-1) infection causes two serious diseases: adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy (HAM). Immunological studies have revealed that HTLV-1 Tax-specific CD8+ cytotoxic T-cells (Tax-CTLs) in asymptomatic carriers (ACs) and ATL patients play an important role in the elimination of HTLV-1-infected host cells, whereas Tax-CTLs in HAM patients trigger an excessive immune response against HTLV-1-infected host cells infiltrating the central nervous system (CNS), leading to local inflammation. Our previous evaluation of HTLV-1 Tax301-309 (SFHSLHLLF)-specific Tax-CTLs (Tax301-309-CTLs) revealed that a unique T-cell receptor (TCR) containing amino acid (AA)-sequence motif PDR, was shared among HLA-A*24:02+ ACs and ATL patients and behaved as an eliminator by strong activity against HTLV-1. However, it remains unclear whether PDR+Tax301-309-CTLs also exist in HLA-A*24:02+ HAM patients and are involved in the pathogenesis of HAM. In the present study, by high-throughput TCR repertoire analysis technology, we revealed TCR repertoires of Tax301-309-CTLs in peripheral blood (PB) of HLA-A*24:02+ HAM patients were skewed, and a unique TCR-motif PDR was conserved in HAM patients (10 of 11 cases). The remaining case dominantly expressed (-DR, P-R, and PD-), which differed by one AA from PDR. Overall, TCRs with unique AA-sequence motifs PDR, or (-DR, P-R, and PD-) accounted for a total of 0.3-98.1% of Tax301-309-CTLs repertoires of HLA-A*24:02+ HAM patients. Moreover, TCR repertoire analysis of T-cells in the cerebrospinal fluid (CSF) from four HAM patients demonstrated the possibility that PDR+Tax301-309-CTLs and (-DR, P-R, and PD-)+Tax301-309-CTLs efficiently migrated and accumulated in the CSF of HAM patients fostering increased inflammation, although we observed no clear significant correlation between the frequencies of them in PB and the levels of CSF neopterin, a known disease activity biomarker of HAM. Furthermore, to better understand the potential function of PDR+Tax301-309-CTLs, we performed immune profiling by single-cell RNA-sequencing of Tax301-309-CTLs, and the result showed that PDR+Tax301-309-CTLs up-regulated the gene expression of natural killer cell marker KLRB1 (CD161), which may be associated with T-cell activation and highly cytotoxic potential of memory T-cells. These findings indicated that unique and shared PDR+Tax301-309-CTLs have a potential role in promoting local inflammation within the CNS of HAM patients.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doenças da Medula Espinal / Linfócitos T Citotóxicos / Vírus Linfotrópico T Tipo 1 Humano / Infecções por HTLV-I Tipo de estudo: Risk_factors_studies Limite: Adult / Humans Idioma: En Revista: Front Immunol Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Japão

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doenças da Medula Espinal / Linfócitos T Citotóxicos / Vírus Linfotrópico T Tipo 1 Humano / Infecções por HTLV-I Tipo de estudo: Risk_factors_studies Limite: Adult / Humans Idioma: En Revista: Front Immunol Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Japão