Identification and tracking of HTLV-1–infected T cell clones in virus-associated neurologic disease
Human T lymphotropic virus type 1–assoicated (HTLV-1–associated) myelopathy/tropical spastic paraparesis (HAM/TSP) is a neuroinflammatory disease caused by the persistent proliferation of HTLV-1–infected T cells. Here, we performed a T cell receptor (TCR) repertoire analysis focused on HTLV-1–infect...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Clinical investigation
2023-04-01
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| Series: | JCI Insight |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/jci.insight.167422 |
| _version_ | 1797634330217938944 |
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| author | Satoshi Nozuma Eiji Matsuura Masakazu Tanaka Daisuke Kodama Toshio Matsuzaki Akiko Yoshimura Yusuke Sakiyama Shingo Nakahata Kazuhiro Morishita Yoshimi Enose-Akahata Steven Jacoboson Ryuji Kubota Hiroshi Takashima |
| author_facet | Satoshi Nozuma Eiji Matsuura Masakazu Tanaka Daisuke Kodama Toshio Matsuzaki Akiko Yoshimura Yusuke Sakiyama Shingo Nakahata Kazuhiro Morishita Yoshimi Enose-Akahata Steven Jacoboson Ryuji Kubota Hiroshi Takashima |
| author_sort | Satoshi Nozuma |
| collection | DOAJ |
| description | Human T lymphotropic virus type 1–assoicated (HTLV-1–associated) myelopathy/tropical spastic paraparesis (HAM/TSP) is a neuroinflammatory disease caused by the persistent proliferation of HTLV-1–infected T cells. Here, we performed a T cell receptor (TCR) repertoire analysis focused on HTLV-1–infected cells to identify and track the infected T cell clones that are preserved in patients with HAM/TSP and migrate to the CNS. TCRβ repertoire analysis revealed higher clonal expansion in HTLV-1–infected cells compared with noninfected cells from patients with HAM/TSP and asymptomatic carriers (ACs). TCR clonality in HTLV-1–infected cells was similar in patients with HAM/TSP and ACs. Longitudinal analysis showed that the TCR repertoire signature in HTLV-1–infected cells remained stable, and highly expanded infected clones were preserved within each patient with HAM/TSP over years. Expanded HTLV-1–infected clones revealed different distributions between cerebrospinal fluid (CSF) and peripheral blood and were enriched in the CSF of patients with HAM/TSP. Cluster analysis showed similarity in TCRβ sequences in HTLV-1–infected cells, suggesting that they proliferate after common antigen stimulation. Our results indicate that exploring TCR repertoires of HTLV-1–infected cells can elucidate individual clonal dynamics and identify potential pathogenic clones expanded in the CNS. |
| first_indexed | 2024-03-11T12:07:05Z |
| format | Article |
| id | doaj.art-dd32f1404890456588f10294cc14d342 |
| institution | Directory Open Access Journal |
| issn | 2379-3708 |
| language | English |
| last_indexed | 2024-03-11T12:07:05Z |
| publishDate | 2023-04-01 |
| publisher | American Society for Clinical investigation |
| record_format | Article |
| series | JCI Insight |
| spelling | doaj.art-dd32f1404890456588f10294cc14d3422023-11-07T16:25:25ZengAmerican Society for Clinical investigationJCI Insight2379-37082023-04-0187Identification and tracking of HTLV-1–infected T cell clones in virus-associated neurologic diseaseSatoshi NozumaEiji MatsuuraMasakazu TanakaDaisuke KodamaToshio MatsuzakiAkiko YoshimuraYusuke SakiyamaShingo NakahataKazuhiro MorishitaYoshimi Enose-AkahataSteven JacobosonRyuji KubotaHiroshi TakashimaHuman T lymphotropic virus type 1–assoicated (HTLV-1–associated) myelopathy/tropical spastic paraparesis (HAM/TSP) is a neuroinflammatory disease caused by the persistent proliferation of HTLV-1–infected T cells. Here, we performed a T cell receptor (TCR) repertoire analysis focused on HTLV-1–infected cells to identify and track the infected T cell clones that are preserved in patients with HAM/TSP and migrate to the CNS. TCRβ repertoire analysis revealed higher clonal expansion in HTLV-1–infected cells compared with noninfected cells from patients with HAM/TSP and asymptomatic carriers (ACs). TCR clonality in HTLV-1–infected cells was similar in patients with HAM/TSP and ACs. Longitudinal analysis showed that the TCR repertoire signature in HTLV-1–infected cells remained stable, and highly expanded infected clones were preserved within each patient with HAM/TSP over years. Expanded HTLV-1–infected clones revealed different distributions between cerebrospinal fluid (CSF) and peripheral blood and were enriched in the CSF of patients with HAM/TSP. Cluster analysis showed similarity in TCRβ sequences in HTLV-1–infected cells, suggesting that they proliferate after common antigen stimulation. Our results indicate that exploring TCR repertoires of HTLV-1–infected cells can elucidate individual clonal dynamics and identify potential pathogenic clones expanded in the CNS.https://doi.org/10.1172/jci.insight.167422InflammationVirology |
| spellingShingle | Satoshi Nozuma Eiji Matsuura Masakazu Tanaka Daisuke Kodama Toshio Matsuzaki Akiko Yoshimura Yusuke Sakiyama Shingo Nakahata Kazuhiro Morishita Yoshimi Enose-Akahata Steven Jacoboson Ryuji Kubota Hiroshi Takashima Identification and tracking of HTLV-1–infected T cell clones in virus-associated neurologic disease JCI Insight Inflammation Virology |
| title | Identification and tracking of HTLV-1–infected T cell clones in virus-associated neurologic disease |
| title_full | Identification and tracking of HTLV-1–infected T cell clones in virus-associated neurologic disease |
| title_fullStr | Identification and tracking of HTLV-1–infected T cell clones in virus-associated neurologic disease |
| title_full_unstemmed | Identification and tracking of HTLV-1–infected T cell clones in virus-associated neurologic disease |
| title_short | Identification and tracking of HTLV-1–infected T cell clones in virus-associated neurologic disease |
| title_sort | identification and tracking of htlv 1 infected t cell clones in virus associated neurologic disease |
| topic | Inflammation Virology |
| url | https://doi.org/10.1172/jci.insight.167422 |
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