Lymphocyte homing to the spleen

描述(申请人提供)：免疫系统的正常功能 取决于T和B细胞之间的相互作用，这种相互作用发生在 次级淋巴器官。为了使同源词相互作用发生 在罕见的抗原特异性T和B细胞之间，必须有大量的细胞 在淋巴器官中循环。而迁移的黏附路径 对淋巴结和Peyer‘s斑块进行了鉴定，没有发现 在向脾迁移的过程中发挥主要作用。使用收养转移 技术，我们已经证明了迁移到淋巴系统的时间过程 脾的T细胞和B细胞各不相同。另外，我们发现， 活化的T淋巴细胞进入脾的白髓是 弱智。此应用程序的目标是提供对 T和B淋巴细胞进入和通过淋巴组织的途径 脾脏的小室。来检验T和B淋巴细胞是 针对脾的淋巴小室，我们建议 三个具体目标：一、确定和描述T和 B淋巴细胞迁移到白髓中；II.鉴定和 描述调节淋巴细胞迁移到 脾白髓；III.测定活化状态对小鼠的影响 淋巴细胞归巢于脾的白髓。实验将涉及到 过继转移纯化淋巴细胞在缺陷小鼠体内的应用 各种黏附分子。过继转移人口的迁移 淋巴细胞将通过活体显微镜实时显示， 扫描共聚焦显微镜。识别脾特异性的抗体 将准备结构并测试其修饰淋巴细胞的能力 这种组织中的迁移行为。两组间淋巴细胞迁移的比较 激活的和未激活的细胞是计划的。我们将使用RNase保护 阐明潜在的趋化因子和受体的分析，这些受体在 归宿。此外，使用转基因方法，各种粘连 分子和趋化因子受体在培养的细胞中过度表达 淋巴细胞。然后这些细胞将被用于过继转移实验 阐明它们在贩运到脾中的作用。身份识别 控制淋巴细胞进入淋巴小室的机制 脾将为免疫调节性药物治疗提供新的靶点。

DESCRIPTION (provided by applicant): Normal function of the immune system depends upon interactions between T and B cells, which take place in the secondary lymphoid organs. In order for the cognate interactions to occur between rare antigen-specific T and B cells, large numbers of cells must circulate through the lymphoid organs. While adhesion pathways for migration to lymph nodes and Peyer's patches have been identified, none has been found to play a major role in migration to the spleen. Using adoptive transfer techniques, we have shown that the time course of migration into the lymphoid compartment of the spleen differs for T and B cells. In addition, we find that entry of activated T lymphocytes into the white pulp of the spleen is retarded. The goal of this application is to provide further insight into the pathways with which T and B lymphocytes migrate into and through the lymphoid compartment of the spleen. To test the hypothesis that T and B lymphocytes are specifically targeted to the lymphoid compartment of the spleen, we propose three specific aims: I. To identify and characterize the locations where T and B lymphocyte migration into the white pulp occurs; II. To identify and characterize key molecules regulating the migration of lymphocytes into the white pulp of the spleen; III. To determine the effect of activation status on lymphocyte homing to the white pulp of the spleen. Experiments will involve adoptive transfer of purified lymphocytes from and into mice deficient in various adhesion molecules. The migration of adoptively transferred lymphocytes will be visualized by intravital microscopy using a real-time, scanning confocal microscope. Antibodies recognizing spleen-specific structures will be prepared and tested for their ability to modify lymphocyte migration behavior in this tissue. Comparison of lymphocyte migration in activated and non-activated cells is planned. We will use RNase protection assays to elucidate potential chemokines and receptors that are important in the homing. Additionally, using a transgene approach, various adhesion molecules, as well as chemokine receptors will be over-expressed in cultured lymphocytes. These cells will then be used in adoptive transfer experiments to illuminate their role in trafficking to the spleen. Identification of mechanisms controlling entry of lymphocytes into the lymphoid compartment of the spleen will provide new targets for immunomodulatory drug therapy.