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HTLV-1, a retrovirus which infects T cells, causes a rare, debilitating neurological disease named HAM/TSP. It is characterized by chronic inflammation of the spinal cord but the underlying mechanism is poorly understood. This study aims to investigate the immunoregulatory mechanisms operating in the spinal cord by utilizing single-cell methods to profile the transcriptome and T cell repertoire of immune cells in the blood and cerebrospinal fluid. We hope to identify key molecules which cause chronic inflammation and identify novel biomarkers to aid decision-making in clinical practice.
We have procured blood (n = 35) and cerebrospinal fluid (CSF) samples (n = 15) from a total of 35 patients. All samples have already been processed using the 10x Chromium Single-cell Immune Profiling platform for gene expression profile as well as enriching for T-cell receptor (TCR) sequences. All libraries are sequenced, and the data was then analysed using the Seurat package in R. We observed results below. 1) The population of CD8+ T-cells and infected CD4+ T-cells are increased in the CSF. 2) Clustering of infected CD4+ T-cells population showed a distinct CSF-predominant cluster with low HTLV-1 sense expression and high HTLV-1 antisense expression. 3) Clonality analysis of T-cell repertoire showed that CD8+ T-cells are more expanded than CD4+ T-cells, both in the blood and CSF. 4) Using a prediction algorithm, we also managed to identify potential TCRs which can bind to Tax epitopes, an immunogenic HTLV-1 protein. 5) When we analysed Tax-specific CD8+ T-cells which was sorted using a Tax dextramer, we found a population which appears to be enriched within the CSF and have differential usage of cytotoxic-related genes. Differential expression analysis identified several potential genes which can be used to identify these population and experiments are currently ongoing to validate these findings.
すべて 2023 2022
すべて 雑誌論文 (3件) (うち国際共著 2件、 査読あり 2件、 オープンアクセス 2件) 学会発表 (5件) (うち国際学会 2件)
Journal of Virology
巻: 97 号: 1
10.1128/jvi.01542-22
Methods in Molecular Biology
巻: - ページ: 259-278
10.1007/978-1-0716-2647-4_17
Frontiers in Immunology
巻: 13 ページ: 01-12
10.3389/fimmu.2022.991928
