B7-2 expression on tumor cells is important for the acquisition of cytotoxic T lymphocyte activity by spleen cells from low-dose-melphalan-treated MOPC-315 tumor bearers via a mechanism that requires either B7-1 or B7-2 expression on host antigen-presenti
B7-2 expression on tumor cells is important for the acquisition of cytotoxic T lymphocyte activity by spleen cells from low-dose-melphalan-treated MOPC-315 tumor bearers via a mechanism that requires either B7-1 or B7-2 expression on host antigen-presenti
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肿瘤细胞上的 B7-2 表达对于低剂量美法仑治疗的 MOPC-315 肿瘤携带者的脾细胞获得细胞毒性 T 淋巴细胞活性非常重要，其机制需要宿主抗原上表达 B7-1 或 B7-2
DOI：
10.1007/s002620050022
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Mokyr,MB
中科院分区：
文献类型：
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作者：
Sojka,DK;LaMotte,RN;Mokyr,MB
我们之前已经证明，B7-2(CD86)和B7-1(CD80)有助于小剂量马法兰(L-苯丙氨酸芥末)在导致肿瘤部位获得强大细胞毒性T淋巴细胞(CTL)活性的条件下对荷大鼠MOPC-315肿瘤的疗效。由于B7-1和B7-2在肿瘤细胞和宿主抗原提呈细胞(APC)上都有表达，本研究旨在探讨肿瘤细胞和宿主APC上各共刺激分子对获得抗MOPC-315 CTL活性的相对重要性。利用 体外系统获得细胞毒性T淋巴细胞活性，我们发现，宿主抗原原细胞上B7的表达对于低剂量马法兰治疗的MOPC315肿瘤患者脾细胞刺激培养中CTL活性的发展是重要的，尽管B7-1或B7-2的表达是足够的。此外，我们发现B7-2在刺激物肿瘤细胞上高水平表达，而不是B7-1在低水平表达，对于CTL活性的获得也是重要的。然而， 在体外对表达B7-2的MOPC315肿瘤细胞刺激所获得的绝大多数CTL活性被发现依赖于表达B7的宿主APC。因此，在MOPC-315肿瘤细胞上高水平表达的B7-2可能促进了MOPC-315刺激肿瘤细胞的快速裂解，从而使肿瘤相关抗原更容易通过表达B7的宿主APC有效地递送，进而刺激低剂量马法兰治疗的MOPC-315肿瘤携带者的脾细胞获得CTL活性。
We have previously shown that B7-2 (CD86) and, to a lesser extent, B7-1 (CD80) contribute to the curative effectiveness of low-dose melphalan (l-phenylalanine mustard) for mice bearing a large MOPC-315 tumor under conditions that lead to the acquisition of potent cytotoxic T lymphocyte (CTL) activity at the tumor site. Since B7-1 and B7-2 are expressed on both tumor cells and host antigen-presenting cells (APC), the current studies were undertaken to examine the relative importance of each costimulatory molecule on tumor cells and on host APC for the acquisition of anti-MOPC-315 CTL activity. Utilizing an in vitro system for the acquisition of CTL activity, we found that B7 expression on host APC is important for the development of CTL activity in stimulation cultures of spleen cells from low-dose-melphalan-treated MOPC-315 tumor bearers, although the expression of either B7-1 or B7-2 is sufficient. In addition, we found that B7-2, which is expressed at high levels on stimulator tumor cells, but not B7-1, which is expressed at much lower levels, is also important for the acquisition of CTL activity. However, the vast majority of the CTL activity acquired in vitro in response to stimulation with the B7-2-expressing MOPC-315 tumor cells was found to depend on B7-expressing host APC. Thus, it is likely that B7-2, which is expressed at high levels on MOPC-315 tumor cells, promotes the rapid lysis of MOPC-315 stimulator tumor cells, thereby making tumor-associated antigens more readily available for efficient presentation by B7-expressing host APC which, in turn, stimulate the acquisition of CTL activity by spleen cells from low-dose-melphalan-treated MOPC-315 tumor bearers.