Reduced frequency, diversity, and function of human T cell leukemia virus type 1-specific CD8+ T cell in adult T cell leukemia patients
Reduced frequency, diversity, and function of human T cell leukemia virus type 1-specific CD8+ T cell in adult T cell leukemia patients
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DOI：
10.4049/jimmunol.177.8.5718
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发表时间：
2006-10-15
影响因子：
4.4
通讯作者：
Sonoda, Shunro
中科院分区：
文献类型：
--
作者：
Kozako, Tomohiro;Arima, Naomichi;Sonoda, Shunro
人类T细胞嗜淋巴病毒1型（HTLV-1）特异性CTL被认为是降低成人T细胞白血病（ATL）风险的免疫效应物。然而，抗htlv -1 CTL在ATL发生前后的体内情况尚未确定。为了表征无症状HTLV-1携带者（AC）和ATL患者的抗HTLV-1 CTL，我们使用HTLV-1 Tax或Env/HLA四聚体的16个不同表位以及细胞内细胞溶解效应分子（ifn - γ、穿孔素和颗粒酶B）分析了35例AC和32例ATL患者PBMC中HTLV-1特异性CD8(+) T细胞的频率和多样性。ATL中tax特异性CD8+ T细胞的总体频率显著低于AC (53% vs 90%, p = 0.001)，而env特异性CD8(+) T细胞的差异无统计学意义。AC具有90%的Tax(11-19)/HLA-A*0201特异性四聚体（+）细胞和92%的Tax(301-309)/HLA-A*2402特异性四聚体（+）细胞。一些AC识别不止一个表位。相比之下，ATL在频率为30%和55%时仅识别HLA-A*0201的Tax（11-19）和HLA-A*2402的Tax（301-309）。AC和ATL结合Tax(11-19)/HLA-A*0201和Tax(301-309)/HLA-A*2402四聚体的细胞百分比也有显著差异。AC和ATL的抗htlv -1 Tax CD8(+) T细胞对Tax产生ifn - γ。相反，ATL抗htlv -1 CD8(+) T细胞的穿孔素和颗粒酶B表达显著低于AC。AC中Tax-specific CD8(+) T细胞的频率与HLA-A*0201的前病毒载量有关。这些结果表明，抗htlv -1 Tax CD8(+) T细胞克隆的频率、多样性和功能降低可能是ATL发生的风险之一。
Human T cell lymphotropic virus type 1 (HTLV-1)-specific CTL are thought to be immune effectors that reduce the risk of adult T cell leukemia (ATL). However, in vivo conditions of anti-HTLV-1 CTL before and after ATL development have yet to be determined. To characterize anti-HTLV-1 CTL in asymptomatic HTLV-1 carriers (AC) and ATL patients, we analyzed the frequency and diversity of HTLV-1-specific CD8(+) T cells in PBMC of 35 AC and 32 ATL patients using 16 distinct epitopes of HTLV-1 Tax or Env/HLA tetramers along with intracellular cytolytic effector molecules (IFN-gamma, perforin, and granzyme B). Overall frequency of subjects possessing Tax-specific CD8+ T cells was significantly lower in ATL than AC (53 vs 90%; p = 0.001), whereas the difference in Env-specific CD8(+) T cells was not statistically significant. AC possessed Tax(11-19)/HLA-A*0201-specific tetramer(+) cells by 90% and Tax(301-309)/HLA-A*2402-specific tetramer(+) cells by 92%. Some AC recognized more than one epitope. In contrast, ATL recognized only Tax(11-19) with HLA-A*0201 and Tax(301-309) with HLA-A*2402 at frequencies of 30 and 55%. There were also significant differences in percentage of cells binding Tax(11-19)/HLA-A*0201 and Tax(301-309)/HLA-A*2402 tetramers between AC and ATL. Anti-HTLV-1 Tax CD8(+) T cells in AC and ATL produced IFN-gamma in response to Tax. In contrast, perforin and granzyme B expression in anti-HTLV-1 CD8(+) T cells of ATL was significant lower than that of AC. Frequency of Tax-specific CD8(+) T cells in AC was related to proviral load in HLA-A*0201. These results suggest that decreased frequency, diversity, and function of anti-HTLV-1 Tax CD8(+) T cell clones maybe one of the risks of ATL development.