Flood P M, Kripke M L, Rowley D A, Schreiber H
Proc Natl Acad Sci U S A. 1980 Apr;77(4):2209-13. doi: 10.1073/pnas.77.4.2209.
Autologous anti-idiotypic responses to tumorspecific lymphocytes altered the capability of mice to reject syngeneic tumors. This was shown by using two non-crossreacting fibrosarcoma lines, 1591 and 1316, induced by ultraviolet light. Cells from these tumor lines are regularly rejected when transplanted into normal syngeneic C3H mice but grow progressively in animals immunosuppressed by irradiation with ultraviolet light or by x-irradiation and thymectomy. Immunization of normal mice with 1591-specific lymphoblasts that had been generated in mixed lymphocyte-tumor cell cultures caused a loss of resistance to 1591 tumor cells, but the animals remained resistant to 1316 tumor cells. In vitro, spleen cells from animals immunized with 1591-specific lymphoblasts did not generate cytolytic T cells to 1591 fibrosarcoma cells, but spleen cells from the same animals responded normally to 1316 fibrosarcoma cells. Furthermore, spleen cells from animals immunized with 1591-specific lymphoblasts contained idiotype-specific T cells that lysed 1591-specific lymphoblasts, whereas 1316-specific lymphoblasts were unaffected. Immunization of normal animals with nonresponding lymphocytes from the same mixed lymphocyte-tumor cell cultures as the 1591-specific lymphoblasts showed normal responses to both tumors in vivo and in vitro. These results suggest that changes in the balance of tumor-specific and anti-idiotypic T lymphocyte clones can influence the capability of an individual to respond effectively to tumor antigens and can determine whether a tumor grows or regresses.
对肿瘤特异性淋巴细胞的自体抗独特型反应改变了小鼠排斥同基因肿瘤的能力。这是通过使用由紫外线诱导产生的两种非交叉反应性纤维肉瘤系1591和1316来证明的。当将来自这些肿瘤系的细胞移植到正常同基因C3H小鼠中时，它们会被正常排斥，但在经紫外线照射或X射线照射及胸腺切除而免疫抑制的动物中会逐渐生长。用在混合淋巴细胞 - 肿瘤细胞培养物中产生的1591特异性淋巴母细胞对正常小鼠进行免疫，导致其对1591肿瘤细胞的抵抗力丧失，但这些动物对1316肿瘤细胞仍保持抗性。在体外，用1591特异性淋巴母细胞免疫的动物的脾细胞不会产生针对1591纤维肉瘤细胞的细胞毒性T细胞，但来自相同动物的脾细胞对1316纤维肉瘤细胞反应正常。此外，用1591特异性淋巴母细胞免疫的动物的脾细胞含有能裂解1591特异性淋巴母细胞的独特型特异性T细胞，而1316特异性淋巴母细胞则不受影响。用与1591特异性淋巴母细胞相同的混合淋巴细胞 - 肿瘤细胞培养物中无反应的淋巴细胞对正常动物进行免疫，结果显示在体内和体外对两种肿瘤均有正常反应。这些结果表明，肿瘤特异性和抗独特型T淋巴细胞克隆平衡的变化可影响个体有效应答肿瘤抗原的能力，并可决定肿瘤是生长还是消退。
