Christensen N D, Kreider J W, Horetsky R L
Department of Pathology, College of Medicine, Pennsylvania State University, Hershey 17033.
Cancer Res. 1988 Feb 15;48(4):943-9.
An antiproliferative suppressor lymphokine was produced from rat T-cells specifically in response to the poorly immunogenic syngeneic mammary adenocarcinoma 13762A. The tumor-induced suppressor lymphokine (TISL) was produced late in culture (peak production on Days 4 and 5) and showed strong but selective inhibitory activity on a variety of immune responses. The immune peritoneal exudate cell response to a highly immunogenic clone from the parental tumor (clone 18A) and the concanavalin A-stimulated response of nonimmune spleen cells were inhibited strongly by TISL. In contrast, the immune spleen cell response to 13762A and the lipopolysaccharide response of nonimmume spleen cells were unaffected. Preliminary molecular weight and physicochemical analysis of TISL indicated that the molecule was large (Mr greater than 350,000); partially sensitive to 75 degrees C treatment for 15 min and to pH 2.0 treatment; only partly degraded by the enzymes trypsin, chymotrypsin, and proteinase K; and completely destroyed by boiling. Although TISL was produced specifically in response to 13762A tumor, prior immunization in vivo was not necessary for the induction of the suppressor lymphokine. These results indicate that populations of rat lymphocytes contain naturally occurring TISL secreting cells, which can be activated specifically by tumor antigens such as those expressed by 13762A.
一种抗增殖抑制性淋巴因子由大鼠T细胞产生，该T细胞是对免疫原性较差的同基因乳腺腺癌13762A产生特异性反应而形成的。肿瘤诱导的抑制性淋巴因子（TISL）在培养后期产生（第4天和第5天产量达到峰值），并对多种免疫反应表现出强烈但具有选择性的抑制活性。TISL强烈抑制免疫腹膜渗出细胞对来自亲代肿瘤的高免疫原性克隆（克隆18A）的反应以及刀豆球蛋白A刺激的非免疫脾细胞反应。相比之下，免疫脾细胞对13762A的反应以及非免疫脾细胞的脂多糖反应未受影响。对TISL的初步分子量和理化分析表明，该分子较大（分子量大于350,000）；对75摄氏度处理15分钟和pH 2.0处理部分敏感；仅被胰蛋白酶、胰凝乳蛋白酶和蛋白酶K部分降解；煮沸可将其完全破坏。尽管TISL是对13762A肿瘤产生特异性反应而产生的，但体内预先免疫对于抑制性淋巴因子的诱导并非必需。这些结果表明，大鼠淋巴细胞群体中含有天然存在的分泌TISL的细胞，这些细胞可被肿瘤抗原如13762A所表达的抗原特异性激活。
