Nishimura M I, Stroynowski I, Hood L, Ostrand-Rosenberg S
Department of Biology, University of Maryland Baltimore County 21228.
J Immunol. 1988 Dec 15;141(12):4403-9.
Recent reports suggested a correlation between decreased expression of tumor cell MHC class I Ag and increased susceptibility to NK cells. These studies led to the hypothesis that tumor cells displaying reduced levels of MHC class I Ag have reduced tumorigenicity in vivo because they are eliminated from the host by endogenous NK cells. The present studies use the murine hepatoma BW7756 and a spontaneous H-2Kb loss variant, Hepa-1, to test this hypothesis. The parental BW7756 tumor is highly malignant in syngeneic C57L/J hosts while Hepa-1 cells do not give rise to tumors, suggesting that the loss of H-2Kb Ag expression correlates with decreased tumorigenicity and NK susceptibility. Hepa-1 cells were therefore transfected with an H-2Kb gene to generate H-2Kb Ag expressing clones. The resulting clones were tested for tumorigenicity. Syngeneic or NK-deficient C57BL/6-beige/beige mice challenged with Hepa-1 or the H-2Kb transfectants rejected the cells, suggesting that reexpression of H-2Kb Ag does not restore tumorigenicity and that NK cells are not involved in Hepa-1 rejection. In vitro H-2Kb Ag-negative and -positive Hepa-1 cells are equally susceptible to tilorone-boosted NK cells, indicating that MHC class I Ag expression also does not affect in vitro NK susceptibility. Tumor challenged athymic nude and sublethally irradiated syngeneic mice develop tumors demonstrating that T cells are probably responsible for rejection of the Hepa-1 tumor, and that H-2Kb Ag expression has no effect on rejection. Inasmuch as the expression of H-2Kb Ag on Hepa-1 cells does not effect tumorigenicity or in vitro NK susceptibility, the previously reported association between reduced MHC class I Ag levels and increased NK susceptibility is not universally applicable.
最近的报告表明，肿瘤细胞MHC I类抗原表达降低与对自然杀伤细胞（NK细胞）的易感性增加之间存在相关性。这些研究提出了一个假说，即MHC I类抗原水平降低的肿瘤细胞在体内的致瘤性降低，因为它们会被内源性NK细胞从宿主体内清除。本研究使用小鼠肝癌BW7756及其自发的H-2Kb缺失变体Hepa-1来验证这一假说。亲代BW7756肿瘤在同基因C57L/J宿主中具有高度恶性，而Hepa-1细胞不会引发肿瘤，这表明H-2Kb抗原表达的缺失与致瘤性降低和NK易感性相关。因此，用H-2Kb基因转染Hepa-1细胞以产生表达H-2Kb抗原的克隆。对所得克隆进行致瘤性测试。用Hepa-1或H-2Kb转染细胞攻击同基因或NK缺陷的C57BL/6-米色/米色小鼠，结果小鼠排斥这些细胞，这表明H-2Kb抗原的重新表达并不能恢复致瘤性，且NK细胞不参与Hepa-1的排斥反应。在体外，H-2Kb抗原阴性和阳性的Hepa-1细胞对替洛隆增强的NK细胞同样敏感，这表明MHC I类抗原表达也不影响体外NK易感性。用肿瘤攻击无胸腺裸鼠和亚致死剂量照射的同基因小鼠，它们会形成肿瘤，这表明T细胞可能是Hepa-1肿瘤排斥反应的原因，且H-2Kb抗原表达对排斥反应没有影响。由于Hepa-1细胞上H-2Kb抗原的表达不影响致瘤性或体外NK易感性，因此先前报道的MHC I类抗原水平降低与NK易感性增加之间的关联并不普遍适用。
