T CELL COLLABORATION IN TUMOR SPECIFIC CTL RESPONSES

描述：（改编自申请人摘要）抗原之间的协作 （Ag）特异性Ic CD 8和CD 4 T细胞对于产生有效的免疫应答至关重要。 抗肿瘤I细胞反应，但很少有人知道在哪里，何时以及如何 这发生了。我们开发了一个模型， Ag特异性T细胞对体内肿瘤生长的响应。该模型采用 来自具有转基因TCR的OT-I小鼠的CD 8 T细胞的过继转移 对Kb/0 VA 257 -264具有特异性，并用E.G7肿瘤攻击 将OVA表达为假肿瘤Ag。宿主CD 4 T细胞对免疫的贡献 已经在功能上证明了OT-I细胞的应答，但是这些 Ag特异性细胞不能被可视化。我们现在正在开发一种模型， 采用OT-1 CD 8 T细胞沿着向正常小鼠的双重过继转移 用来自具有特异性针对CD 4 T细胞的转基因TCR的OT-II小鼠的CD 4 T细胞， I-Ad/OVA323-339.使用该模型来可视化，定量和表征 在对E.G7肿瘤的应答过程中，我们将 追求四个具体目标：（1）描述协作互动， 发生在Ag特异性CD 8和CD 4 T细胞之间， 肿瘤特异性反应。(2)为了确定CTLA-4阻断在 允许有效的抗肿瘤T细胞应答。(3)检测CD 8和CD 4 T细胞 免疫中的细胞协作以保护免受肿瘤和 记忆反应中的协作。新的免疫策略， 我们实验室最近的工作将被检查。(4)描述各种方法的特点 通过克服T细胞耐受性来进行肿瘤免疫治疗。我们预计 在拟议的研究中获得的结果将有助于更好的基础 了解CD 4和CD 8 T细胞在免疫中的协作 对癌症的反应，并可能提出新的方法， 治疗性免疫策略。

DESCRIPTION: (Adapted from applicant's abstract) Collaboration between antigen (Ag).specific Ic CD8 and CD4 T cells is critical for generating an effective ant-tumor I cell response, yet very little is known about where, when and how this occurs. We have developed a model that has allowed us to visualize Ag-specific T cells responding to tumor growing in vivo. The model employs adoptive transfer of CD8 T cells from 0T-I mice having a transgenic TCR specific for Kb/0VA257-264 into normal mice, and challenge with E.G7 tumor expressing OVA as a pseudo-tumor Ag. A contribution of host CD4 T cells to the response of the 0T-I cells has been demonstrated functionally, but these Ag-specific cells cannot be visualized. We are now developing a model that employs double adoptive transfer into normal mice of OT-1 CD8 T cells along with CD4 T cells from 0T-II mice having a transgenic TCR specific for I-Ad/OVA323-339. Using this model to visualize, quantitate and characterize the OVA-specific T cells during the course of a response to E.G7 tumor we will pursue four specific aims: (1) To describe the collaborative interactions that occur between Ag-specific CD8 and CD4 T cells during the course of a tumor-specific response. (2) To determine the role of CTLA-4 blockade in allowing effective anti-tumor T cell responses. (3) To examine CD8 and CD4 T cell collaboration in immunization for protection against tumor and the collaboration in the memory response. Novel immunization strategies based on recent work in our laboratory will be examined. (4) To characterize approaches for tumor immunotherapy by overcoming T cell tolerance. We anticipate that the results obtained in the proposed studies will contribute to a better basic understanding of the collaboration between CD4 and CD8 T cells in the immune response to cancer, and may suggest novel approaches for protective and therapeutic immunization strategies.