Functional Diversity in Pre-Immune Helper T Cells

描述（由申请方提供）：Th细胞是获得性免疫的主要调节因子，对蛋白抗原免疫的抗原特异性B细胞应答的质量具有关键影响。我们最近集中在一个表型划分存在于免疫前Th细胞隔室，原来有实质性的影响抗原驱动的Th细胞在体内的功能。基于Ly6C表达的Th细胞表型分裂起源于胸腺成熟，并与Th细胞的免疫前TCR库的不均匀分配相关。在用抗原免疫之前，具有不同TCR谱但对相同外源肽表位具有特异性的初始Th细胞分类为Ly6Ch1和Ly6Cl0。以这种方式，可以将两组单独的初始Th细胞募集到对相同外源抗原的应答中。我们试图了解这种外周细胞命运分裂对体内抗原特异性B细胞免疫发展的影响。 了解免疫前功能多样性对Th细胞调节的B细胞免疫的发展的作用具有根本意义，对疫苗设计的公共卫生倡议具有潜在的高度影响。在我们的初步研究中，我们证明了在初级B细胞应答中，每个Th细胞亚群促进浆细胞发育的能力存在实质性差异。这些数据表明，不同的Th细胞亚群开发不同的Th效应功能，也可能建立独特的记忆Th细胞隔室。我们将确定Ly6Chi和Ly6Clo Th细胞对B细胞免疫（SAI）的影响。研究这些Th细胞亚群及其后代如何调节适应性免疫（萨尔）将是重要的。最后，我们将评估先天免疫如何控制两个Th细胞亚群和效应功能（SAIII）的发展。

DESCRIPTION (provided by applicant): Th cells are the master regulators of adaptive immunity and have critical impact on the quality of antigen-specific B cell responses to protein antigen immunization. We have recently focused on a phenotypic divide that exists in the pre-immune Th cell compartment that turns out to have substantial impact on antigen-driven Th cell function in vivo. The Th cell phenotypic divide based on Ly6C expression, has its origins in thymic maturation and correlates with the uneven assortment of the pre-immune TCR repertoire for Th cells. Naive Th cells with different TCR profiles, but specificity for the same foreign peptide epitope, assort Ly6Chi and Ly6CIo prior to immunization with the antigen. In this manner, two separate sets of naive Th cells can be recruited into the response to the same foreign antigen. We seek to understand the impact of this peripheral cell fate division on the development of antigen-specific B cell immunity in vivo. Understanding the role of pre-immune functional diversity on the development of Th cell-regulated B cell immunity is of fundamental interest with potentially high impact on the public health initiative of vaccine design. In our initial studies, we demonstrate a substantial difference in the capacity of each Th cell subset to promote plasma cell development in the primary B cell response. These data suggest that the different Th cell subsets develop distinct Th effector functions and may also establish unique memory Th cell compartments. We will determine the impact of Ly6Chi and Ly6CIo Th cells on B cell immunity (SAI). It will be important to examine how these Th cell subsets and their progeny regulate adaptive immunity (SAll). Finally, we will evaluate how innate immunity controls the two Th cell subsets and development of effector function (SAIII).