Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
PLoS Pathog. 2010 May 27;6(5):e1000924. doi: 10.1371/journal.ppat.1000924.
NK and gammadelta T cells can eliminate tumor cells in many experimental models, but their effect on the development of tumors caused by virus infections in vivo is not known. Polyomavirus (PyV) induces tumors in neonatally infected mice of susceptible strains and in adult mice with certain immune deficiencies, and CD8+ alphabeta T cells are regarded as the main effectors in anti-tumor immunity. Here we report that adult TCRbeta knockout (KO) mice that lack alphabeta but have gammadelta T cells remain tumor-free after PyV infection, whereas TCRbeta x delta KO mice that lack all T cells develop tumors. In addition, E26 mice, which lack NK and T cells, develop the tumors earlier than TCRbeta x delta KO mice. These observations implicate gammadelta T and NK cells in the resistance to PyV-induced tumors. Cell lines established from PyV-induced tumors activate NK and gammadelta T cells both in culture and in vivo and express Rae-1, an NKG2D ligand. Moreover, these PyV tumor cells are killed by NK cells in vitro, and this cytotoxicity is prevented by treatment with NKG2D-blocking antibodies. Our findings demonstrate a protective role for NK and gammadelta T cells against naturally occurring virus-induced tumors and suggest the involvement of NKG2D-mediated mechanisms.
自然杀伤细胞和γδ T 细胞可以在许多实验模型中消除肿瘤细胞，但它们对体内病毒感染引起的肿瘤发展的影响尚不清楚。多瘤病毒（PyV）可诱导易感品系新生感染小鼠和某些免疫缺陷成年小鼠发生肿瘤，CD8+αβ T 细胞被认为是抗肿瘤免疫的主要效应细胞。在这里，我们报告说，缺乏αβ但具有γδ T 细胞的成年 TCRβ 敲除（KO）小鼠在 PyV 感染后仍保持无肿瘤状态，而缺乏所有 T 细胞的 TCRβ x δ KO 小鼠则会发生肿瘤。此外，缺乏 NK 和 T 细胞的 E26 小鼠比 TCRβ x δ KO 小鼠更早发生肿瘤。这些观察结果表明 γδ T 和 NK 细胞参与了对 PyV 诱导的肿瘤的抵抗。从 PyV 诱导的肿瘤中建立的细胞系在培养和体内均能激活 NK 和 γδ T 细胞，并表达 Rae-1，一种 NKG2D 配体。此外，这些 PyV 肿瘤细胞在体外可被 NK 细胞杀伤，而用 NKG2D 阻断抗体处理可预防这种细胞毒性。我们的研究结果表明 NK 和 γδ T 细胞对自然发生的病毒诱导肿瘤具有保护作用，并提示涉及 NKG2D 介导的机制。
