Vallera D A, Mentzer S J, Maizel S E
Cancer Res. 1982 Feb;42(2):397-404.
Sponge matrices surgically implanted in the s.c. space of the back of normal BALB/c mice were injected with a "regressor" dose of Moloney virus-induced BALB/c tumor cells. The kinetics of the generation of cytotoxic cells within the sponge was studied over a 22-day period in a short-term 51Cr release assay. Cytotoxic activity peaked on Day 16 and then declined to negligible levels by Day 22. No cytotoxicity was detectable when nontransformed BALB/c blast cells, Moloney leukemia virus-induced tumor (LSTRA) cells, or unrelated chemically induced tumor (EL4) cells were used as targets. When the cellular composition of implanted tumor sponges was examined on Day 16, it was found to be 30 to 40% myeloperoxidase-positive cells, 15 to 25% surface immunoglobulin-positive cells, and 40 to 50% theta-positive cells. Treatment with anti-Thy 1.2 plus complement eliminated the cytotoxic response on Day 16. The ratio of T-cells to tumor cells within the sponge was determined by immunofluorescence. Kinetic studies showed that the number of theta-positive cells increased well before cytolytic activity was detected, possibly reflecting increasing numbers of amplifier T-cells or cytotoxic cell precursors. A later decline in theta-positive cells correlated directly with decreased cytotoxicity. Furthermore, onset of cytotoxic activity also correlated with a decline in the percentage of Moloney murine sarcoma virus tumor cells within the sponge. Sponge cells isolated on Day 16 (peak cytotoxicity), mixed with lethal dosages of moloney murine sarcoma virus tumor cells, successfully neutralized the lethal challenge demonstrating the in vivo antitumor efficacy of these effector cells. Sponges were also implanted in mice which had been immunized with single injection of Moloney murine sarcoma virus cells. Inoculation of the sponge with tumor cells resulted in a second set response in which cytotoxic cells appeared much earlier than in unsensitized animals. Cells from spleen, lymph node, or peritoneal cavity of normal or presensitized animals with tumor sponge implants were not cytotoxic, suggesting a highly localized response.
将莫洛尼病毒诱导的BALB/c肿瘤细胞的“消退剂”剂量注射到手术植入正常BALB/c小鼠背部皮下空间的海绵基质中。在短期51Cr释放试验中，在22天的时间内研究了海绵内细胞毒性细胞产生的动力学。细胞毒性活性在第16天达到峰值，然后在第22天下降到可忽略不计的水平。当未转化的BALB/c胚细胞、莫洛尼白血病病毒诱导的肿瘤（LSTRA）细胞或无关的化学诱导肿瘤（EL4）细胞用作靶细胞时，未检测到细胞毒性。在第16天检查植入肿瘤海绵的细胞组成时，发现其为30%至40%的髓过氧化物酶阳性细胞、15%至25%的表面免疫球蛋白阳性细胞和40%至50%的θ阳性细胞。用抗Thy 1.2加补体处理消除了第16天的细胞毒性反应。通过免疫荧光测定海绵内T细胞与肿瘤细胞的比例。动力学研究表明，θ阳性细胞的数量在检测到细胞溶解活性之前就显著增加，这可能反映了放大T细胞或细胞毒性细胞前体数量的增加。随后θ阳性细胞的减少与细胞毒性的降低直接相关。此外，细胞毒性活性的开始也与海绵内莫洛尼鼠肉瘤病毒肿瘤细胞百分比的下降相关。在第16天（细胞毒性峰值）分离的海绵细胞与致死剂量的莫洛尼鼠肉瘤病毒肿瘤细胞混合，成功中和了致死性攻击，证明了这些效应细胞的体内抗肿瘤功效。海绵也植入了单次注射莫洛尼鼠肉瘤病毒细胞免疫的小鼠体内。用肿瘤细胞接种海绵导致二次反应，其中细胞毒性细胞出现的时间比未致敏动物早得多。正常或预致敏动物植入肿瘤海绵后，脾脏、淋巴结或腹腔的细胞没有细胞毒性，表明反应高度局限。
