Long-term persistence of limited HTLV-I Tax-specific cytotoxic T cell clones in a patient with adult T cell leukemia/lymphoma after allogeneic stem cell transplantation.
Long-term persistence of limited HTLV-I Tax-specific cytotoxic T cell clones in a patient with adult T cell leukemia/lymphoma after allogeneic stem cell transplantation.
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成人 T 细胞白血病/淋巴瘤患者在同种异体干细胞移植后，有限的 HTLV-I Tax 特异性细胞毒性 T 细胞克隆长期持续存在。
DOI：
10.1007/s10875-012-9729-5
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发表时间：
2012
期刊：
影响因子：
9.1
通讯作者：
et al.
中科院分区：
文献类型：
--
作者：
Tanaka Y;Nakasone H;Yamazaki R;Kanda Y;et al.
目的成人T细胞白血病/淋巴瘤（ATL）是由人T细胞嗜淋巴病毒1型（HTLV-1）引起的高度侵袭性T细胞恶性肿瘤。最近的临床研究表明，同种异体干细胞移植（HSCT）通过利用移植物抗ATL效应改善ATL的临床病程，并且供体来源的HTLV-1 Tax-specific CD8+细胞毒性T细胞（ctl）有助于HSCT后移植物抗ATL效应。然而，对于接受HSCT的ATL患者中Tax-specific ctl的免疫学特性知之甚少。方法从单细胞水平对ATL患者造血干细胞移植后外周血（PB）和骨髓（BM）配对样本中Tax-specific ctl的频率、分化、功能和克隆动态进行分析。我们使用流式细胞术和单细胞T细胞受体（TCR）库分析方法，无需培养步骤。结果供体来源的特异性ctl至少在HSCT后慢性移植物抗宿主病期间有效地抑制了HTLV-1在PB和BM中的复制。此外，税收特异性ctl在BM和PB之间具有可比性，除了优先在BM而不是PB中积累。基于CD27+、CD28+/−和CD57+/−的主要表型，税收特异性ctl作为低分化的cd45ra - ccr7效应记忆ctl持续存在。我们的方法使用单细胞TCR库分析方法显示，税收特异性CTL的寡克隆反应高度受限，表达两种主要CTL克隆的TCR BV7-或BV30-在HSCT后的三年内持续存在，并在PB和BM中保持对HTLV-1的强细胞毒活性。结论税收特异性ctl的研究结果为今后ATL的免疫治疗研究提供了新的方向。
PurposeAdult T cell leukemia/lymphoma (ATL) is a highly aggressive malignancy of T cells caused by human T cell lymphotropic virus type 1 (HTLV-1). Recent clinical studies have suggested that allogeneic stem cell transplantation (HSCT) improves the clinical course of ATL by harnessing a graft-versus-ATL effect, and that donor-derived HTLV-1 Tax-specific CD8+cytotoxic T cells (CTLs) contribute to the graft-versus-ATL effect after HSCT. However, little is known about the immunological characteristics of Tax-specific CTLs in ATL patients who underwent HSCT.MethodsWe serially analyzed frequencies, differentiation, functions and clonal dynamics of Tax-specific CTLs in paired samples of peripheral blood (PB) and bone marrow (BM) from an ATL patient after HSCT at the single-cell level. We used flowcytometric and single-cell T cell receptor (TCR) repertoire analysis methods without culture steps.ResultsDonor-derived Tax-specific CTLs effectively suppressed HTLV-1 replication in both PB and BM at least during chronic graft-versus-host disease after HSCT. Furthermore, Tax-specific CTLs had comparable properties between BM and PB, except for preferential accumulation in BM rather than PB. Tax-specific CTLs persistently existed as less-differentiated CD45RA-CCR7-effector memory CTLs based on predominant phenotypes of CD27+, CD28+/−and CD57+/−. Our approach using single-cell TCR repertoire analysis method showed highly restricted oligoclonal responses of Tax-specific CTLs, and TCR BV7- or BV30- expressing two predominant CTL clones persistently existed and maintained strong cytotoxic activities against HTLV-1 in both PB and BM over three years after HSCT.ConclusionsThese findings about Tax-specific CTLs provide insights into future directions for studies on immunotherapy against ATL.