T cell immune response to group A streptococci in NALT

描述（由申请人提供）：仅在美国，每年就有500万人被诊断为链球菌性咽炎，每年有1200-1500人死于A群链球菌（GAS）感染的并发症。这个项目的总体目标是了解细胞和免疫学的原因，高达三分之一的儿童大力治疗咽炎继续脱落链球菌，为什么更多的人没有产生可测量的免疫反应。我们的研究将利用一个完善的鼻内感染小鼠模型来模拟人类扁桃体的感染。初步结果表明，GAS对BalBc鼻下淋巴组织（NALT）有明显的趋向性。将采用转基因的、幼稚的卵清蛋白特异性CD4 T细胞过继转移，研究在小鼠鼻内感染表面表达卵抗原的野生型和突变型GAS后，体内基于T细胞的免疫应答。实验将确定感染对NALT和其他淋巴器官抗原特异性T细胞反应的影响。

DESCRIPTION (provided by applicant): Five million people are annually diagnosed with streptococcal pharyngitis, and 1200-1500 die annually from complications of group A streptococcal (GAS) infections in the United States alone. The over all goal of this projection is to understand the cellular and immunological reason that up to a third of children vigorously treated for pharyngitis continue to shed streptococci and why even more fail to develop a measurable immune response. Our in investigation will make use of a well-developed intranasal infection murine model to mimic infection of human tonsils. Preliminary results show that GAS have an efficient tropism for lymphoid tissue (NALT) beneath nasal passages of BalBc. Adoptive transfer of transgenic, naive ovalbumin specific CD4 T cells will be used to study the T cell based immune response in vivo following intranasal infection of mice with wild type and mutant strains of GAS that expresses the Ova antigen on their surface. Experiments will determine impact of infection on the antigen specific T cell response in NALT and other lymphoid organs.