Perforin-mediated cytotoxicity is critical for surveillance of spontaneous lymphoma.
Perforin-mediated cytotoxicity is critical for surveillance of spontaneous lymphoma.
复制标题
穿孔素介导的细胞毒性对于监测自发淋巴瘤至关重要。
DOI：
10.1084/jem.192.5.755
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发表时间：
2000-09-04
期刊：
影响因子：
--
通讯作者：
Trapani JA
中科院分区：
文献类型：
--
作者：
Smyth MJ;Thia KY;Street SE;MacGregor D;Godfrey DI;Trapani JA
细胞毒性淋巴细胞对癌症的免疫监视已经假设了几十年，但细胞毒性淋巴细胞在预防自发性恶性肿瘤中的作用的直接证据一直缺乏。由于细胞毒性T淋巴细胞和自然杀伤细胞对许多实验性癌症的排斥依赖于穿孔蛋白（pfp），我们研究了pfp缺陷小鼠对癌症易感性的增加。在这里，我们表明，pfp缺陷小鼠在不同的淋巴细胞谱系（T，B，NKT）的恶性肿瘤的发病率很高，这表明一个特定的要求pfp在保护淋巴瘤的发生。同时缺乏p53基因表达加重了对淋巴瘤的易感性，p53基因突变通常也易患人类恶性肿瘤，包括淋巴瘤。相反，在p53缺陷小鼠中，肉瘤的发病率和发病年龄不受影响。与肿瘤排斥反应由CD 8 + T淋巴细胞控制的免疫活性小鼠相比，Pfp缺陷小鼠在移植时对这些淋巴瘤的易感性至少高1,000倍。这项研究是第一个涉及直接细胞毒性的淋巴细胞调节淋巴瘤。
Immune surveillance by cytotoxic lymphocytes against cancer has been postulated for decades, but direct evidence for the role of cytotoxic lymphocytes in protecting against spontaneous malignancy has been lacking. As the rejection of many experimental cancers by cytotoxic T lymphocytes and natural killer cells is dependent on the pore-forming protein perforin (pfp), we examined pfp-deficient mice for increased cancer susceptibility. Here we show that pfp-deficient mice have a high incidence of malignancy in distinct lymphoid cell lineages (T, B, NKT), indicating a specific requirement for pfp in protection against lymphomagenesis. The susceptibility to lymphoma was accentuated by simultaneous lack of expression of the p53 gene, mutations in which also commonly predispose to human malignancies, including lymphoma. In contrast, the incidence and age of onset of sarcoma was unaffected in p53-deficient mice. Pfp-deficient mice were at least 1,000-fold more susceptible to these lymphomas when transplanted, compared with immunocompetent mice in which tumor rejection was controlled by CD8+ T lymphocytes. This study is the first that implicates direct cytotoxicity by lymphocytes in regulating lymphomagenesis.
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影响因子：
64.8
作者：
DONEHOWER, LA;HARVEY, M;BRADLEY, A
通讯作者：
BRADLEY, A
影响因子：
5.4
作者：
Matloubian, M;Suresh, M;Ahmed, R
通讯作者：
Ahmed, R
影响因子：
64.8
作者：
KAGI, D;LEDERMANN, B;HENGARTNER, H
通讯作者：
HENGARTNER, H
影响因子：
15.3
作者：
SMYTH, MJ;ORTALDO, JR;YOUNG, HA
通讯作者：
YOUNG, HA
影响因子：
5.4
作者：
KAWASAKI, A;SHINKAI, Y;OKUMURA, K
通讯作者：
OKUMURA, K