Identification and tracking of HTLV-1–infected T cell clones in virus-associated neurologic disease

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Abstract

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.

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