Gresser I, Carnaud C, Maury C, Sala A, Eid P, Woodrow D, Maunoury M T, Belardelli F
Institut de Recherches Scientifiques sur le Cancer, Centre National de la Recherche Scientifique, Villejuif, France.
J Exp Med. 1991 May 1;173(5):1193-203. doi: 10.1084/jem.173.5.1193.
DBA/2 mice were injected intravenously with 2 x 10(6) 3C18 Friend erythroleukemia cells (FLC), a cell line resistant to interferon alpha/beta (IFN-alpha/beta). Although daily administration of mouse IFN-alpha/beta markedly increased the mean survival time, most IFN-treated mice continued to harbor FLC in different organs. To investigate the mechanisms responsible for this persistent suppression of FLC growth in IFN-treated mice, we undertook a series of adoptive transfer experiments with sera and spleen cells. Sera from FLC-injected, IFN-treated mice were very effective in conferring protection on DBA/2 mice even when injected systemically (intravenously) 18-24 h before intravenous challenge with FLC. These sera also exhibited antitumor activity when injected subcutaneously or intraperitoneally together with FLC. The protective factor in serum was shown to be an immunoglobulin. FLC-injected, IFN-treated mice developed antibodies to FLC demonstrable by radioimmunoassay and complement-dependent cytotoxicity. Sera from these mice recognized a specific 65-kD FLC membrane antigen(s) not detectable on membrane extracts from RBL-5 or ESb tumor cells, or on normal spleen cells. FLC-injected, IFN-treated mice also developed a specific cellular response demonstrable by transfer of protection with spleen cells injected intravenously or subcutaneously. Analysis of the responsible spleen cell populations indicated that the effector cells were neither T nor B cells. These results demonstrating the importance of host humoral and cellular immune mechanisms in the persistent suppression of FLC in IFN-treated mice may be relevant to the use of IFN-alpha/beta in patients in whom tumors may regress and tumor cells may then remain latent for extended periods of time.
给DBA/2小鼠静脉注射2×10⁶个3C18弗氏红白血病细胞（FLC），该细胞系对α/β干扰素（IFN-α/β）具有抗性。尽管每日给予小鼠IFN-α/β可显著延长平均存活时间，但大多数经IFN治疗的小鼠在不同器官中仍持续存在FLC。为了研究IFN治疗的小鼠中FLC生长持续受到抑制的机制，我们进行了一系列血清和脾细胞的过继转移实验。来自注射FLC并经IFN治疗的小鼠的血清，即使在静脉注射FLC进行攻击前18 - 24小时全身（静脉）注射，也能非常有效地为DBA/2小鼠提供保护。当与FLC一起皮下或腹腔注射时，这些血清也表现出抗肿瘤活性。血清中的保护因子被证明是一种免疫球蛋白。注射FLC并经IFN治疗的小鼠产生了可通过放射免疫测定和补体依赖性细胞毒性检测到的针对FLC的抗体。这些小鼠的血清识别一种特定的65-kD FLC膜抗原，在RBL-5或ESb肿瘤细胞的膜提取物或正常脾细胞上无法检测到。注射FLC并经IFN治疗的小鼠还产生了一种特定的细胞反应，可通过静脉或皮下注射脾细胞进行保护转移来证明。对相关脾细胞群体的分析表明，效应细胞既不是T细胞也不是B细胞。这些结果表明宿主体液和细胞免疫机制在IFN治疗的小鼠中对FLC的持续抑制中起重要作用，这可能与α/β干扰素在肿瘤可能消退且肿瘤细胞可能随后长时间潜伏的患者中的应用有关。
