Tfh是一类新发现的CD4+T细胞亚群，其主要功能是参与生发中心形成，辅助B细胞产生抗体，参与体液免疫应答。目前，研究表明用乳酸菌作为口服疫苗载体预防禽流感病毒（AIV）有很好的应用前景。申请人已构建融合表达AIV保守抗原NP-M1-DCpep的乳酸菌，发现其免疫小鼠和雏鸡不仅能产生显著的特异性SIgA抗体，还有很好的保护效果,从而推测这与小鼠淋巴结中增加的Tfh有密切联系，但其机制有待深入揭示。据此，本项目拟利用流式细胞术、MHC肽四聚体、基因敲除小鼠和雏鸡模型等技术和手段，从新功能型乳酸菌调节DCs和特异性Tfh活化、介导特异性Tfh促进生发中心形成和抗体产生以及抗AIV感染效应等方面开展研究，以期阐明新功能型乳酸菌通过特异性Tfh诱导SIgA产生的免疫学机制，为基于新功能型乳酸菌的疫病免疫防控新策略提供理论依据。

Follicular helper T cells (Tfh), defined as subset of CD4+ T cells recently, were found critical role in germinal centers (GCs) formation, providing help to B cells for the production of antibodies and humoral immunity responses. At present, many reportes show that it is a very good prospect to use lactic acid bacteria as oral vaccine vector to prevent AIV. Our previously study confirmed that a novel lactic acid bacteria (nLAB) was constructed by using Lactobacillus plantarum to deliver AIV protective antigen (NP-M1) via specific dendritic cell-targeting peptides to dendritic cells (DCs), which elicited high levels of specific sIgA antibodies and induced robust protective immunity against AIV. The immune response induced by nLAB may associate with high number of Tfh in lymph node. However, the mechanism of this protection effect remains unclear. Therefore, the purpose of our research is to investigate the mechanism of how nLAB mediate Tfh cells to protect host under AIV challenge. We will evaluate and illustrate DCs, specific Tfh activity and differentiation, their influence on GC formation and production of antibodies. Flow cytometry, IAbNP MHCII tetramer and infection model of knockout mice and chickens will be implemented in our study. The aim is to understand the underlying mechanism of nLAB in inducing the production of SIgA by specific Tfh cells, and provide theoretical and experimental bases for developing new technology of immune prevention by nLAB.