REJUVENATION OF THE T-CELL COMPARTMENT IN AGING PRIMATES

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。次级项目的主要支助 子项目的主要研究者可能是由其他来源提供的， 包括其他NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 免疫系统的老化伴随着对广泛病原体的免疫防御减弱，特别是那些宿主以前没有遇到过的病原体。在临床上，这与传染病发病率和死亡率的增加有关，而传染病一直是65岁及65岁以上人群的五大死因之一。目前，免疫衰老的原因和干预措施尚未明确。其中最一致和最显着的年龄相关的变化是那些发生在T细胞的稳态和功能。随着年龄的增长，T细胞免疫力的严重缺陷已经得到了很好的证明，重要的是，改善T细胞功能通常会恢复老年动物的免疫防御，认为T细胞缺陷在免疫衰老中起着关键作用。T细胞老化的主要标志包括幼稚T细胞的丧失和效应记忆T细胞的积累。由于胸腺退化和外周T细胞亚群维持失调，T细胞产生减少。纳乌通常负责防御新的和重新出现的病原体的原始T细胞群体受到这种失调的严重影响，并且恢复原始T细胞的产生和维持被广泛认为是对抗免疫衰老的关键目标。因此，该提案的目标是测试两种生长因子KGF和IL-7单独和组合的能力，以改善老年人的幼稚T细胞产生和维持。在本研究的第一年，我们已经完成了4个实验，以确定IL-7或KGF的能力，扩大幼稚（和记忆）外周T细胞室在RM。 IL-7已被证明通过外周（非胸腺）机制瞬时扩增幼稚T细胞区室。 IL-7还起到扩大中央记忆区室的作用，并且这些作用更持久。 KGF在迄今为止进行的研究中尚未证明有效，但目前正在等待高剂量研究的结果。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Aging of the immune system is accompanied by weakening of immune defense against a wide spectrum of pathogens, particularly those that have not been previously encountered by the host. This clinically correlates with increased morbidity and mortality from infectious diseases, which consistently rank in the top five causes of death amongst those 65 and older. Neither the causes of, nor the points of intervention against, immune senescence has been defined at the present. Amongst the most consistent and most dramatic age-related changes are those that occur in T-cell homeostasis and function. Profound defects in T-cell immunity with aging have been well documented, and, importantly, improving T-cell function usually restores immune defense in aged animals, arguing that T-cell defects play a key role in immune aging. Cardinal signs of T-cell aging include loss of na¿ve and accumulation of effector memory T-cells. There is diminished T-cell production due to thymic involution and dysregulated maintenance of peripheral T-cell subsets. Na¿ve T-cell populations, which are normally in charge of defending against new and re-emerging pathogens, are dramatically affected by this dysregulation, and restoration of na¿ve T-cell production and maintenance is widely considered to be a crucial goal in combating immune senescence. The goals of this proposal are therefore to test the ability of two growth factors, KGF and IL-7, alone and in combination, to improve na¿ve T-cell production and maintenance in old age. In the first year of this study we have completed 4 experiments to determine the ability of IL-7 or KGF to expand the na¿ve (and memory) peripheral T cell compartment in RM. IL-7 has been demonstrated to transiently expand the na¿ve T cell compartment via a peripheral (non-thymic) mechanism. IL-7 also acts to expand the central memory compartment and these effects are more prolonged. KGF has not proven effective in the studies performed to date, but results of a high dose study are currently pending.