Goronzy Jörg J, Weyand Cornelia M
Kathleen B and Mason I Lowance Center for Human Immunology, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
Curr Opin Immunol. 2005 Oct;17(5):468-75. doi: 10.1016/j.coi.2005.07.020.
The T cell system is a complex and highly dynamic system that is amazingly robust over many decades of human life. Its functional competence is determined not only by its size but also by its diversity. Homeostatic control mechanisms have to secure sufficient T cell replenishment while preventing loss of clonal diversity. Major homeostatic challenges include profound expansion and shrinkage of T cell clonotypes upon antigenic triggering and, more importantly, age-related changes in T cell regeneration. The ability of the thymus to rebuild a diverse repertoire ceases in the fifth decade of life. Emerging data suggest that the end of the 7th decade of life defines a critical time period when T cell homeostasis is no longer guaranteed and diversity of the naïve T-cell repertoire collapses. Thus, failure of T cell homeostasis appears to result from cumulative defects of T cell generation. Elucidation of the underlying mechanisms will allow for extending this turning point to later in life; ultimately, interventions have to aim at restoring thymic function and complementary modes of T cell reconstitution.
T细胞系统是一个复杂且高度动态的系统，在人类数十年的生命历程中，它惊人地强健。其功能能力不仅取决于其规模，还取决于其多样性。稳态控制机制必须确保足够的T细胞补充，同时防止克隆多样性的丧失。主要的稳态挑战包括抗原触发后T细胞克隆型的深度扩增和收缩，更重要的是，T细胞再生中与年龄相关的变化。胸腺重建多样化库的能力在生命的第五个十年停止。新出现的数据表明，生命第七个十年末期定义了一个关键时期，此时T细胞稳态不再有保障，幼稚T细胞库的多样性崩溃。因此，T细胞稳态的失败似乎是由T细胞生成的累积缺陷导致的。阐明潜在机制将有助于把这个转折点推迟到生命后期；最终，干预措施必须旨在恢复胸腺功能和T细胞重建的补充模式。
