Attenuation of CD8+ T-cell function by CD4+CD25+ regulatory T cells in B-cell non-Hodgkin's lymphoma
Attenuation of CD8+ T-cell function by CD4+CD25+ regulatory T cells in B-cell non-Hodgkin's lymphoma
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DOI：
10.1158/0008-5472.can-06-1822
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发表时间：
2006-10-15
期刊：
影响因子：
11.2
通讯作者：
Ansell, Stephen M.
中科院分区：
文献类型：
--
作者：
Yang, Zhi-Zhang;Novak, Anne J.;Ansell, Stephen M.
肿瘤细胞对CTL介导的凋亡具有抗性的潜在机制尚不清楚。使用B细胞非霍奇金淋巴瘤（B细胞NHL）的人类模型，我们发现肿瘤内T-reg细胞抑制活化的自体浸润性CD 8（+）T细胞的增殖和颗粒产生。我们的研究结果还表明，肿瘤内Treg细胞的存在完全减弱了暴露于淋巴瘤B细胞的浸润性CD 8（+）T细胞的脱粒和随后的细胞毒活性。此外，我们发现，肿瘤内T-reg细胞数量的增加与B细胞NHL患者活检标本中的CD 8（+）T细胞数量相关，支持肿瘤内T-reg细胞抑制浸润性CD 8（+）T细胞增殖的体外研究结果。总之，这些数据表明，人淋巴瘤B细胞对自体CTL介导的细胞死亡敏感，但受到肿瘤内T-reg细胞抑制功能的保护。
The underlying mechanisms by which tumor cells are resistant to CTL-mediated apoptosis are not clear. Using a human model of B-cell non-Hodgkin's lymphoma (B-cell NHL), we show that intratumoral T-reg cells inhibit the proliferation and granule production of activated autologous infiltrating CD8(+) T cells. Our results also show that degranulation and subsequent cytotoxic activity of infiltrating CD8(+) T cells exposed to lymphoma B cells is completely attenuated by the presence of intratumoral Treg cells. Furthermore, we show that increased numbers of intratumoral T-reg cells correlates with the number of CD8(+) T cells in biopsy specimens from patients with B-cell NHL, supporting the in vitro findings that intratumoral T-reg cells inhibit proliferation of infiltrating CD8(+) T cells. Taken together, these data indicate that human lymphoma B cells are sensitive to autologous CTL-mediated cell death but are protected by the inhibitory function of intratumoral T-reg cells.