Lymphocyte homing to the spleen

描述（由申请人提供）：免疫系统的正常功能 依赖于T和B细胞之间的相互作用，这发生在 次级淋巴器官 为了使同源相互作用发生 在罕见的抗原特异性T细胞和B细胞之间， 通过淋巴器官循环。虽然迁移的粘附途径 淋巴结和派伊尔淋巴结的淋巴结转移， 在向脾脏的迁移中起主要作用。使用过继转移 技术，我们已经表明，迁移到淋巴细胞的时间过程， 脾的隔室对于T和B细胞是不同的。此外，我们发现， 活化的T淋巴细胞进入脾的白色髓是 弱智此应用程序的目标是提供对 T和B淋巴细胞迁移进入和通过淋巴样组织的途径 脾的隔室。为了检验T和B淋巴细胞是 特异性靶向脾脏淋巴区室，我们建议 三个具体目标：一。为了识别和表征T和 发生B淋巴细胞迁移到白色牙髓中; II.识别和 表征调节淋巴细胞迁移到 脾的白色髓; III.确定激活状态对 淋巴细胞归巢到脾的白色髓。实验将涉及 将纯化的淋巴细胞过继转移至缺乏 各种 粘附 分子。 的 迁移 过继转移 淋巴细胞将通过活体显微镜使用实时， 扫描 共焦 显微镜 抗体 认识 脾特异性 将制备结构并测试它们修饰淋巴细胞的能力， 这种组织中的迁移行为。淋巴细胞迁移的比较 激活和未激活的细胞。我们将使用RNase保护 用于阐明潜在的趋化因子和受体的测定， 归航 此外，使用转基因方法， 分子，以及趋化因子受体将在培养的 淋巴细胞然后将这些细胞用于过继转移实验， 阐明了它们在脾脏运输中的作用。 鉴定 控制淋巴细胞进入淋巴区室的机制 脾脏将为免疫调节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.