Itoh K, Platsoucas C D, Tilden A B, Pollock R E, Balch C M
Cell Immunol. 1987 Sep;108(2):283-96. doi: 10.1016/0008-8749(87)90213-9.
We investigated the lysis of fresh human solid tumor cells by peripheral blood T lymphocytes in the presence of lectins and anti-CD3 monoclonal antibodies (mAb). Addition of certain lectins (Con A, PHA, or WGA) directly into the 4-hr 51Cr-release assay caused significant lysis of (P less than 0.001) noncultured solid tumor targets by enriched populations of granular lymphocytes (GL). Significant levels (P at least less than 0.001) of Con A- or PHA-dependent solid tumor lysis by GL-enriched lymphocytes were observed in 32 of 39 donors (82%) and 14 of 20 donors (70%), respectively. In contrast, the addition of other lectins (PNA, PWM, or LPS) or anti-CD3 mAb did not cause cytotoxicity. The levels of Con A-dependent lysis were comparable to those of interleukin 2 (IL-2)-induced lysis by Leu 11b+ natural killer (NK) cells. The presence of lectins at the effector phase, but not of recombinant IL-2 (rIL-2), was required for the lysis of solid tumor targets. Both Con A-dependent and rIL-2-induced lysis were totally inhibited by treatment of the effector cells with the lysosomotropic agent L-leucine methyl ester (LeuOMe). Effector cells responsible for Con A-dependent lysis of solid tumors expressed T3 (CD3), T8 (CD8), and Leu 7 antigens, but lacked T4 (CD4) and Leu 11 (CD16) antigens as determined by both negative and positive cell selection studies. Con A-dependent lysis was inhibited at the effector phase by anti-CD3 (OKT3 or anti-Leu 4) or anti-CD2 (OKT11) mAb. On the basis of their phenotype (Leu 7+ CD3+ CD8+ CD16-), we hypothesize that these effector cells may contain a population of cytotoxic T cells (CTL) generated in vivo against autologous modified cells that can lyse fresh solid tumor target cells under conditions where the recognition requirements for the CTL are bypassed by lectin approximation.
我们研究了在外周血T淋巴细胞存在凝集素和抗CD3单克隆抗体（mAb）的情况下，新鲜人实体瘤细胞的裂解情况。将某些凝集素（刀豆球蛋白A、植物血凝素或小麦胚芽凝集素）直接添加到4小时的51Cr释放试验中，可导致富集的颗粒淋巴细胞（GL）对未培养的实体瘤靶细胞产生显著裂解（P<0.001）。在39名供体中的32名（82%）和20名供体中的14名（70%）中，分别观察到富集GL的淋巴细胞对刀豆球蛋白A或植物血凝素依赖性实体瘤的显著裂解水平（P至少<0.001）。相比之下，添加其他凝集素（花生凝集素、美洲商陆丝裂原或脂多糖）或抗CD3 mAb不会引起细胞毒性。刀豆球蛋白A依赖性裂解水平与白细胞介素2（IL-2）诱导的Leu 11b+自然杀伤（NK）细胞裂解水平相当。实体瘤靶细胞的裂解需要在效应阶段存在凝集素，而不是重组IL-2（rIL-2）。用溶酶体促渗剂L-亮氨酸甲酯（亮氨酸甲酯）处理效应细胞可完全抑制刀豆球蛋白A依赖性和rIL-2诱导的裂解。通过阴性和阳性细胞分选研究确定，负责刀豆球蛋白A依赖性实体瘤裂解的效应细胞表达T3（CD3）、T8（CD8）和Leu 7抗原，但缺乏T4（CD4）和Leu 11（CD16）抗原。抗CD3（OKT3或抗Leu 4）或抗CD2（OKT11）mAb在效应阶段抑制刀豆球蛋白A依赖性裂解。基于它们的表型（Leu 7+ CD3+ CD8+ CD16-），我们推测这些效应细胞可能包含一群在体内针对自体修饰细胞产生的细胞毒性T细胞（CTL），这些细胞在凝集素近似绕过CTL识别要求的条件下能够裂解新鲜的实体瘤靶细胞。
