Maas R A, Becker M J, Weimar I S, De Nooy J C, Dullens H F, Den Otter W D
University Hospital Utrecht, Department of Pathology, The Netherlands.
Immunobiology. 1993 Jul;188(3):281-92. doi: 10.1016/s0171-2985(11)80236-6.
DBA/2 mice were inoculated i.p. with syngeneic SL2 lymphoma or P815 mastocytoma on day 0 and treated i.p. with 20,000 units IL-2/day on day 10-14. This treatment is curative for 70-90% of the tumor bearing mice. Peritoneal cells and/or spleen cells were isolated from responding mice at the last day of IL-2 therapy. The in vivo antitumor activity of these cells was tested in Winn Assays (i.p.) and by adoptive transfer (i.v.) into mice injected s.c. with tumor previously. Peritoneal exudate cells isolated on day 14 (PEC14) from mice cured of SL2 tumor were highly effective in Winn Assays. Up to 5 x 10(7) SL2 cells could be eliminated in naive mice when injected i.p. together with 2 x 10(7) PEC14. Adoptive transfer (i.v.) of PEC14, without the addition of IL-2, into mice s.c. injected with SL2 tumor cells 1 or 3 days earlier, also prevented outgrowth of the tumor cells. T cells isolated from the spleens were less effective. Only at E:T ratios of 100:1 and 10:1 was tumor outgrowth inhibited. The adoptive transfer of PEC14 resulted in a long lasting immunity of the recipient mice. Furthermore, it was shown that depletion of both the CD8+ and CD4+ T cells from the suspensions used in the transfer studies, resulted in a significant decrease of tumor inhibition. However, the effect was not abrogated completely. PEC14 isolated from IL-2-treated DBA/2 mice cured of P815 tumor, protected naive mice against P815 tumor at E:T ratio 20:1. Adoptive transfer (i.v.) of these PEC14 into mice bearing s.c. P815 did not have an antitumor effect. In conclusion, low dose i.p. IL-2 therapy predominantly induces locally both CD4+ and CD8+ T cells with a strong antitumor activity in vivo. The potency of the IL-2-induced immunity seems related to the type of tumor used.
在第0天给DBA/2小鼠腹腔注射同基因的SL2淋巴瘤或P815肥大细胞瘤，并在第10 - 14天每天腹腔注射20,000单位白细胞介素-2。这种治疗方法可使70 - 90%的荷瘤小鼠治愈。在白细胞介素-2治疗的最后一天，从有反应的小鼠中分离出腹腔细胞和/或脾细胞。这些细胞的体内抗肿瘤活性在温氏试验（腹腔内）以及通过过继转移（静脉内）到先前皮下注射过肿瘤的小鼠中进行测试。从治愈SL2肿瘤的小鼠在第14天分离出的腹腔渗出细胞（PEC14）在温氏试验中非常有效。当与2×10⁷个PEC14一起腹腔注射时，在未接触过肿瘤的小鼠中最多可消除5×10⁷个SL2细胞。在1天或提前3天皮下注射SL2肿瘤细胞的小鼠中，不添加白细胞介素-2而将PEC14静脉内过继转移，也可防止肿瘤细胞生长。从脾脏分离出的T细胞效果较差。仅在效应细胞与靶细胞比例为100:1和10:1时肿瘤生长才受到抑制。PEC14的过继转移使受体小鼠产生持久的免疫力。此外，研究表明，在转移研究中使用的细胞悬液中去除CD8⁺和CD4⁺T细胞，会导致肿瘤抑制作用显著降低。然而，这种效果并未完全消除。从经白细胞介素-２治疗治愈P815肿瘤的DBA/2小鼠中分离出的PEC14，在效应细胞与靶细胞比例为20:1时可保护未接触过肿瘤的小鼠免受P815肿瘤侵害。将这些PEC14静脉内过继转移到皮下携带P815肿瘤的小鼠中没有抗肿瘤作用。总之，低剂量腹腔内白细胞介素-2治疗主要在局部诱导具有强大体内抗肿瘤活性的CD4⁺和CD8⁺T细胞。白细胞介素-2诱导的免疫效力似乎与所用肿瘤的类型有关。
