Characterization of HTLV-1 specific CTLs detected in HAM patients

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08494
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54030:Infectious disease medicine-related
• Research Institution: Kumamoto University
• Principal Investigator: Sugata Kenji 熊本大学, ヒトレトロウイルス学共同研究センター, 講師 (10650616)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: HTLV-1 / HAM / HLA-A24 / Tax / 特異的CD8T細胞

Outline of Final Research Achievements

To understand pathogenesis of HTLV-1-associated inflammatory diseases, we performed integrated single cell analysis using in peripheral blood and cerebrospinal fluid (CSF) cells derived from HAM/TSP patients. Among various cell types, CD8 T cells were increased in the CSF and contained significantly expanded anti-Tax cytotoxic T-lymphocytes (CTLs). Transcriptome analysis demonstrated that anti-Tax CTLs in the CSF showed reduced activation whereas enhanced pro-apoptotic and exhausted phenotype. Furthermore, we found that HLA-A24 presents two different peptides of Tax depending on Tax genotypes. That affects results of HLA multiuser staining in specific CD8 T cells of the infected patients

Free Research Field

腫瘍免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究ではHAM患者の脊髄病変に浸潤しているHTLV-1抗原特異的CTLの遺伝子発現プロファイルに基づき、末梢血での同CTLが発現するHAMの発症リスク遺伝子を発見することを目的としている。HTLV-1特異的CTLが発現するHAMの発症リスク遺伝子を探索するため、次世代シークエンサーを用いて脳脊髄液中のCTLの1細胞遺伝子発現解析とTCRレパトア解析を行った。TCR-CDR3やclonotypeに基づき脳脊髄液中のHTLV-1特異的CTLとの比較を行うことでHAMの発症リスク遺伝子群の発見を目指し、それらを利用してHAMの早期発見・治療開始に繋げる。