2022 Fiscal Year Annual Research Report
Single-cell immune profiling of peripheral blood and cerebrospinal fluid of HAM/TSP patients for elucidation of immunoregulatory mechanisms and novel biomarker discovery
| Project/Area Number |
22K20776
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| Research Institution | Kumamoto University |
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Principal Investigator |
TAN BENJY・JEK・YANG 熊本大学, ヒトレトロウイルス学共同研究センター, 特任助教 (20966882)
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| Project Period (FY) |
2022-08-31 – 2023-03-31
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| Keywords | TLV-1 / HAM/TSP / Immune regulation / Biomarker |
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| Outline of Annual Research Achievements |
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.
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[Journal Article] Clone Dynamics and Its Application for the Diagnosis of Enzootic Bovine Leukosis2022
Author(s)
Md Belal Hossain, Tomoko Kobayashi, Sakurako Makimoto, Misaki Matsuo, Kohei Nishikaku, Benjy Jek Yang Tan, Akhinur Rahman, Samiul Alam Rajib, Kenji Sugata, Nagaki Ohnuki, Masumichi Saito, Toshiaki Inenaga, Kazuhiko Imakawa and Yorifumi Satou
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Journal Title
Journal of Virology
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Pages: -
DOI
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[Presentation] HTLV-1 infection promotes excessive T cell activation and transformation into adult T cell leukemia / lymphoma2022
Author(s)
Tan BJY, Sugata K, Reda O, Matsuo M, Uchiyama K, Miyazato P, Hahaut V, Yamagishi M, Uchimaru K, Suzuki Y, Ueno T, Suzushima H, Katsuya H, Tokunaga M, Uchiyama Y, Nakamura H, Sueoka E, Utsunomiya A, Ono M, Satou Y
Organizer
The 20th International Conference on Human Retrovirology HTLV and related viruses
Int'l Joint Research
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