Coleman Clenton, Howell Koko, Hobbs Monte V, Riggs James E
Department of Biology, Rider University, 2083 Lawrenceville Road, Lawrenceville, NJ 08648-3099, USA.
Immunobiology. 2006;211(9):701-9. doi: 10.1016/j.imbio.2006.03.004. Epub 2006 Jun 9.
Study of immune senescence is complicated by low numbers of antigen-specific lymphocytes, particularly naïve T (Tn)cells which disappear with aging. Although T cell receptor (TCR) transgenic mice facilitate aging research, their large number of Ag-specific T cells renders their T cell pool abnormal, precluding normal in vivo immunity. To create a physiologically relevant model with measurable numbers of TCR transgenic CD4+ T cells in the context of normal lymphocytes, mixed (DO11.10+BALB/c) bone marrow (BM) chimeras were constructed. As found in normal mice, the total number of transgenic T cells and the Tn:memory T cell ratio declined with the aging of the BM chimeras. Although these shifts in T cell subsets were evident in both the lymph nodes and the spleen (SP), they were more pronounced in the SP. Unlike DO11.10 mice, transgenic T cells in the chimera acquired an effector/memory phenotype upon antigen challenge. These results reveal a pliable model to study the impact of the constriction of the Tn cell repertoire upon optimal vaccine responses in the elderly.
免疫衰老的研究因抗原特异性淋巴细胞数量较少而变得复杂，尤其是随着衰老而消失的初始T（Tn）细胞。尽管T细胞受体（TCR）转基因小鼠有助于衰老研究，但其大量的抗原特异性T细胞使其T细胞库异常，排除了正常的体内免疫。为了在正常淋巴细胞的背景下创建一个具有可测量数量的TCR转基因CD4 + T细胞的生理相关模型，构建了混合（DO11.10 + BALB / c）骨髓（BM）嵌合体。正如在正常小鼠中发现的那样，转基因T细胞的总数以及Tn：记忆T细胞比率随着BM嵌合体的衰老而下降。尽管这些T细胞亚群的变化在淋巴结和脾脏（SP）中均很明显，但在SP中更为明显。与DO11.10小鼠不同，嵌合体中的转基因T细胞在受到抗原攻击后获得了效应/记忆表型。这些结果揭示了一个灵活的模型，用于研究Tn细胞库收缩对老年人最佳疫苗反应的影响。
