Avila-Carino J, Torsteinsdottir S, Bejarano M T, Klein G, Klein E, Masucci M G
Department of Tumor Biology, Karolinska Institute, Stockholm, Sweden.
Cell Immunol. 1988 Dec;117(2):303-11. doi: 10.1016/0008-8749(88)90120-7.
Cell lines derived from Epstein-Barr virus (EBV)-positive and EBV-negative Burkitt lymphoma (BL) have a low or defective expression of polymorphic HLA class I determinants compared to EBV-transformed lymphoblastoid cell lines (LCL) of normal B cell origin and are resistant to lysis by cytotoxic T lymphocytes (CTL) specific for the corresponding determinants (M. G. Masucci, S. Torsteinsdottir, J. Colombani, C. Brautbar, E. Klein, and G. Klein, Proc. Natl. Acad. Sci. USA 84, 4567, 1987; S. Torsteinsdottir, C. Brautbar, E. Klein, G. Klein, and M. G. Masucci, Int. J. Cancer, 41, 913, 1988). In order to investigate whether this phenotypic trait of the tumor cells can be modulated by agents known to enhance HLA class I antigen expression, pairs of LCL and BL lines were cultured in the presence of recombinant human interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha. Three low HLA A11 expressor EBV-negative BL lines, DG 75, BL 28, and BL 41, reacted significantly stronger with the anti-HLA A11 monoclonal antibody (Mab) AUF 5.13 after combined treatment with 500 U/ml IFN-gamma and 500 U/ml TNF-alpha. Reactivity with the AUF 5.13 and with other anti-polymorphic class I Mab's was up-regulated also in in vitro EBV-converted sublines of BL 28 and BL 41. The increment of antigen expression depended on the baseline expression in untreated cells. It was largest for the low expressor lines and decreased proportionally to the level of up-regulation induced by EBV conversion. Up-regulation of HLA A11 was accompanied by induction of sensitivity to HLA A11-specific CTLs in BL 28 and its converted subline E95A BL28 while BL 41 and E95A BL 41 remained resistant. The treatment did not affect significantly HLA A11 expression of two EBV-carrying, low HLA A11 expressor BL lines, WW-1-BL and WW-2-BL, and of the EBV-carrying BL 72 line that had a high spontaneous expression. The results suggest that the down-regulation of class I antigen expression is reversible in some but not all BL lines.
与源自正常B细胞的EB病毒（EBV）转化的淋巴母细胞系（LCL）相比，源自EBV阳性和EBV阴性伯基特淋巴瘤（BL）的细胞系多态性HLA-I类决定簇的表达较低或存在缺陷，并且对针对相应决定簇的细胞毒性T淋巴细胞（CTL）介导的裂解具有抗性（M.G.马苏奇、S.托尔斯泰因斯多蒂尔、J.科隆巴尼、C.布劳特巴、E.克莱因和G.克莱因，《美国国家科学院院刊》84, 4567, 1987；S.托尔斯泰因斯多蒂尔、C.布劳特巴、E.克莱因、G.克莱因和M.G.马苏奇，《国际癌症杂志》，41, 913, 1988）。为了研究肿瘤细胞的这种表型特征是否可被已知能增强HLA-I类抗原表达的药物所调节，将LCL和BL细胞系对在重组人干扰素（IFN）-γ和肿瘤坏死因子（TNF）-α存在的情况下进行培养。三个低HLA A11表达的EBV阴性BL细胞系，DG 75、BL 28和BL 41，在与500 U/ml IFN-γ和500 U/ml TNF-α联合处理后，与抗HLA A11单克隆抗体（Mab）AUF 5.13的反应明显增强。在BL 28和BL 41的体外EBV转化亚系中，与AUF 5.13以及其他抗多态性I类Mab的反应性也上调。抗原表达的增加取决于未处理细胞中的基线表达。对于低表达细胞系增加最大，并且与EBV转化诱导的上调水平成比例下降。HLA A11的上调伴随着BL 28及其转化亚系E95A BL28对HLA A11特异性CTL敏感性的诱导，而BL 41和E95A BL 41仍然具有抗性。该处理对两个携带EBV、低HLA A11表达的BL细胞系WW-1-BL和WW-2-BL以及具有高自发表达的携带EBV的BL 72细胞系的HLA A11表达没有显著影响。结果表明，I类抗原表达的下调在一些但不是所有的BL细胞系中是可逆的。
