The dual nature of specific immunological activity of tumor-derived gp96 preparations.
The dual nature of specific immunological activity of tumor-derived gp96 preparations.
复制标题
DOI：
10.1084/jem.189.9.1437
复制
发表时间：
1999-05-03
期刊：
影响因子：
--
通讯作者：
Srivastava PK
中科院分区：
文献类型：
--
作者：
Chandawarkar RY;Wagh MS;Srivastava PK
用最佳剂量的自体肿瘤来源的gp96免疫的小鼠抵抗了gp96来源的肿瘤的攻击。大于最佳剂量5-10倍的gp96免疫不能引起肿瘤免疫。这种效应的缺乏被证明是一种活跃的抗原特异性效应，因为用高剂量的肿瘤来源的gp96免疫，而不是正常组织来源的gp96免疫，会下调抗肿瘤免疫反应。此外，分次接种gp96疫苗所引起的反应种类和水平与相当于分次接种总剂量的单次接种相同。对于肿瘤保护剂量和高下调剂量的gp96都是如此。高剂量gp96免疫小鼠后，其下调活性可通过CD4+而非CD8+ T淋巴细胞过继转移。这些观察结果表明，gp96免疫诱导高度调节的免疫反应，根据免疫条件的不同，导致肿瘤免疫或下调。
Mice immunized with optimal doses of autologous tumor–derived gp96 resist a challenge with the tumor that was the source of gp96. Immunization with quantities of gp96 5–10 times larger than the optimal dose does not elicit tumor immunity. This lack of effect is shown to be an active, antigen-specific effect, in that immunization with high doses of tumor-derived gp96, but not normal tissue–derived gp96, downregulates the antitumor immune response. Furthermore, immunization with fractionated doses of gp96 elicits the same kind and level of response as elicited by a single dose equivalent to the total of the fractionated doses. This is true of the tumor-protective doses as well as the high downregulatory doses of gp96. The downregulatory activity can be adoptively transferred by CD4+ but not CD8+ T lymphocytes from mice immunized with high doses of gp96. These observations indicate that immunization with gp96 induces a highly regulated immune response that, depending upon the conditions of immunization, results in tumor immunity or downregulation.