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...

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Bibliographic Details
Main Authors: 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
Format: Article
Language:English
Published: American Society for Clinical investigation 2023-04-01
Series:JCI Insight
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Online Access:https://doi.org/10.1172/jci.insight.167422
Description
Summary: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.
ISSN:2379-3708