The influence of age on CD4 helper activity

描述（由申请人提供）：年龄对CD4辅助细胞活性的影响。在老年人中，预防流感等高度传染性传染病的疫苗的效力大大降低。这一点极为重要，因为与年轻人相比，老年人因流感住院和死亡的风险要高得多。许多研究试图通过检查老化T细胞的功能来解决这个问题。这些先前的研究的缺点是，他们使用了来自老年小鼠的异质T细胞群，这与在年轻小鼠中发现的T细胞群大不相同。这使得解释这些实验变得困难，因为年龄可能会影响T细胞总数的许多方面。事实上，在年轻人和老年人中，极有可能存在抗原特异性CD4细胞数量的巨大差异。这也可以解释在年轻人和老年人的辅助功能中观察到的差异。老年小鼠免疫后GC形成减少，抗体亲和成熟减少。

DESCRIPTION (provided by the applicant): The influence of age on CD4 helper activity. The efficacy of vaccines for highly contagious infections, such as influenza, are greatly decreased in the elderly. This is extremely important since elderly persons exhibit a much increased risk of hospitalization and death from influenza compared to younger persons. Numerous studies have attempted to address this issue by examining the function of aged T cells. The drawback of these previous studies is that they employed heterogeneous populations of T cells from aged mice which are quite different from T cell populations found in young mice. This makes interpretation of these experiments difficult, since age may affect many aspects of the total T cell population. In fact, it is highly likely that there are dramatically different numbers of antigen-specific CD4 cells in young and aged populations. This may also account for the differences that have been observed in young and aged helper function. Aged mice have been shown to exhibit decreased GC formation and reduced antibody affinity maturation upon immunization. The goal of this application is to use a TCR Tg model to determine what aspects of aged CD4 function contribute to decreased B cell helper activity. This will allow us to directly compare the cognate helper activity of homogeneous populations of Tg CD4 cells from young and aged mice. In this model, naive Tg CD4 cells from aged mice produce less IL-2 upon TCR stimulation compared to young cells. Decreased IL-2 production leads to reduced expansion and subsequent effector generation, as well as reduced CD4OL expression. If we can determine the mechanism of decreased GC formation and subsequent reduction in antibody titers in the aged, we can then begin to examine methods for improvement and, ultimately, increase the efficacy of vaccination in the aged.