Mucosal Lymphocyte Homing in the Head and Neck

产品说明：我们以前的研究表明，鼻相关淋巴组织（NALT）和各种头颈淋巴结（LN）表达独特的地址素模式。来自这些淋巴组织的高内皮微静脉（HEV）与广泛存在MAdCAM-1的派伊尔集合淋巴结（PP）HEV不同。相反，外周淋巴结地址素（PNAd）在这些组织中占主导地位，这表明粘膜淋巴细胞归巢的另一种模式，特别是根据其他研究人员过去的研究显示，粘膜B细胞迁移到小肠固有层（iLP）依赖于MAdCAM- 1-α 4 β 7相互作用，并且在较小程度上依赖于L-选择素。事实上，效应B细胞免疫与α 4 β 7/高表型分离。在本申请中，我们提出存在至少两个不是α 4 β 7/高的其它粘膜B细胞亚群，一个B细胞亚群被鉴定为L-选择素/低α 4 β 7/低，另一个鉴定为α E β 7+。在小鼠鼻内（i.n.）用霍乱毒素（CT）免疫后，我们主要显示L-选择素/低α 4 β 7/低效应B细胞存在于鼻道（NP）、生殖道（RT）和颌下腺（SMG）中。i.n.的评价CT免疫的L-选择素缺陷小鼠显示NP中不存在粘膜效应B细胞，但iLP应答维持为α E β 7+，而不是α 4 β 7/高。总的来说，这些数据表明，L-选择素是重要的抗原（Ag）特异性效应B细胞在非肠粘膜组织中的迁移。因此，该提议将表征L-选择素低α 4 β 7/低和α E β 7 +B细胞在i.n.或口服CT免疫。特定目标1的研究将确定L-选择素和α 4 β 7对i. n.后诱导和效应B细胞免疫的发展的相对重要性。或口服免疫。特定目标2中的研究将确定所述新型L-选择素/低α 4 β 7/低或α E β 7 + B细胞是否可以归巢到非肠以及肠粘膜效应组织。特定目标3的研究将确定哪种B细胞亚群，L-选择素/低α 4 β 7/低或α E β 7+，对i.n.挑战CT从这项工作中，我们将了解如何免疫接种途径可以用来有效地靶向疫苗的非肠粘膜网站。

DESCRIPTION: Work from our previous studies has shown that the nasal-associated lymphoid tissue (NALT) and the various head and neck lymph nodes (LN) express unique addressin patterns. The high endothelial venules (HEV) from these lymphoid tissues do not resemble Peyer's patch (PP) HEV with the extensive presence of MAdCAM-1. Instead, the peripheral node addressin (PNAd) dominates these tissues, suggesting an alternative mode of mucosal lymphocyte homing especially in light of past studies by other investigators showing that mucosal B cell migration to small intestinal lamina propria (iLP) is dependent upon MAdCAM- 1-alpha4beta7 interactions, and to a lesser degree, upon L-selectin. In fact, effector B cell immunity segregated with the alpha4beta7/high phenotype. Herein this application, we propose that at least two other mucosal B cell subsets exist that are not alpha4beta7/high.One B cell subset is identified as L-selectin/low alpha4beta7/low, the other, alphaEbeta7+. In mice intranasally (i.n.) immunized with cholera toxin (CT), we show primarily L-selectin/low alpha4beta7/low effector B cells in the nasal passages (NP), reproductive tract (RT), and submaxillary gland (SMG). Evaluation of i.n. CT-immunized L-selectin-deficient mice show an absence of mucosal effector B ceils in the NP, but iLP responses were maintained as alphaEbeta7+, not alpha4beta7/high. Collectively, these data suggest that L-selectin is important for the migration of antigen (Ag)-specific effector B cells in nonintestinal mucosal tissues. Thus, this proposal will characterize the functional attributes of L-selectinlow alpha4beta7/low and alphaEbeta7+B cells subsequent to i.n. or oral immunization with CT. Studies in Specific Aim 1 will determine the relative importance of L-selectin and alpha4beta7 to the development of both inductive and effector B cell immunity subsequent to i.n. or oral immunization. Studies in Specific Aim 2 will determine determine if the described novel L-selectin/low alpha4beta7/low or alphaEbeta7+ B cells can home to nonintestinal as well as intestinal mucosal effector tissues. Studies in Specific Aim 3 will determine which B cell subset, L-selectin/low alpha4beta7/low or alphaEbeta7+, is protective against i.n. challenge with CT. From this work, we will learn how routes of immunizations can be used to effectively target vaccines to nonintestinal mucosal sites.