Dennert G, Crowley C, Kouba J, Lotan R
J Natl Cancer Inst. 1979 Jan;62(1):89-94.
The ability of retinoic acid (RA), a potent antitumor agent, to stimulate cell-mediated cytotoxicity (CMC) in mice was investigated. Low doses of RA (5-300 micrograms/mouse/day) administered ip into C57BL/6 mice for 5 days daily or for 1--3 months three times a week before immunization in vivo or in vitro with allogeneic BALB/c S194 myeloma cells led to an enhanced cytotoxic activity of their spleen effector cells. Similarly, in a syngeneic situation injection of RA into C57BL/6 or BALB/c mice before in vitro challenge with EL 4 (C57BL/6) or S194 (BALB/c) tumor cells strongly stimulated CMC. The enhanced cytotoxic activity was effected by thymus-derived lymphocytes (T-cells) and specific for the H-2 histocompatibility antigens in the case of the allogeneic sensitization or specific for tumor antigens in the case of the syngeneic sensitization. Because RA had no effect on the effector step of CMC, RA likely enhanced the induction step of T-CMC. The action of RA was antigen-dependent, and it is therefore a true adjuvant rather than a nonspecific stimulator or polyclonal activator of cytotoxic T-cells.
研究了一种强效抗肿瘤剂维甲酸（RA）刺激小鼠细胞介导细胞毒性（CMC）的能力。在体内或体外以同种异体BALB/c S194骨髓瘤细胞免疫C57BL/6小鼠之前，每天腹腔注射低剂量RA（5 - 300微克/小鼠/天），持续5天，或每周三次，持续1 - 3个月，可增强其脾效应细胞的细胞毒性活性。同样，在同基因情况下，在体外以EL 4（C57BL/6）或S194（BALB/c）肿瘤细胞攻击之前，向C57BL/6或BALB/c小鼠注射RA可强烈刺激CMC。增强的细胞毒性活性由胸腺来源的淋巴细胞（T细胞）介导，在同种异体致敏情况下对H-2组织相容性抗原具有特异性，在同基因致敏情况下对肿瘤抗原具有特异性。由于RA对CMC的效应步骤没有影响，RA可能增强了T-CMC的诱导步骤。RA的作用是抗原依赖性的，因此它是一种真正的佐剂，而不是细胞毒性T细胞的非特异性刺激剂或多克隆激活剂。
