Chakravarti B, Abraham G N
Department of Medicine and Center on Aging, University of Rochester Cancer Center, University of Rochester Medical Center, NY 14642, USA.
Mech Ageing Dev. 1999 May 17;108(3):183-206. doi: 10.1016/s0047-6374(99)00009-3.
Changes in the T-lymphocyte compartment represent the most critical component of immunological aging. Recent studies have demonstrated that the age-related decline in T-cell-mediated immunity is a multifactorial phenomenon affecting T-cell subset composition as well as several proximal events such as protein tyrosine phosphorylation, generation of second messengers, calcium mobilization and translocation of protein kinase C, and distal events such as lymphocyte proliferation and cytokine production of the T-cell activation pathway. Age-related T-cell immune deficiency is preceded by thymic involution and is influenced by several intrinsic as well as extrinsic factors. Further, the role of monocytes and macrophages in T-cell activation changes with advancing age. This brief review will summarize the current knowledge of the cellular as well as molecular aspects of immunodeficiency of T cells due to aging, some of the paradoxes of aging as related to T-cell-mediated immunity, and possible factors which contribute to this paradox. Finally, experimental approaches will be suggested that might resolve these controversies and that might provide insights into the diverse and complex mechanisms that contribute to immunodeficiency of T cells. Ultimately these studies may suggest possible therapeutic interventions to enhance immune function in the elderly.
T淋巴细胞区室的变化是免疫衰老最关键的组成部分。最近的研究表明,与年龄相关的T细胞介导免疫功能下降是一种多因素现象,它影响T细胞亚群组成以及一些近端事件,如蛋白酪氨酸磷酸化、第二信使的产生、钙动员和蛋白激酶C的转位,还有远端事件,如淋巴细胞增殖和T细胞激活途径中的细胞因子产生。与年龄相关的T细胞免疫缺陷先于胸腺退化,并受多种内在和外在因素影响。此外,单核细胞和巨噬细胞在T细胞激活中的作用会随着年龄的增长而变化。这篇简短的综述将总结目前关于衰老导致T细胞免疫缺陷的细胞和分子方面的知识、与T细胞介导免疫相关的衰老的一些矛盾之处,以及导致这种矛盾的可能因素。最后,将提出一些实验方法,这些方法可能解决这些争议,并可能深入了解导致T细胞免疫缺陷的多样而复杂的机制。最终,这些研究可能会提出增强老年人免疫功能的可能治疗干预措施。