Naïve and memory CD4 and CD8 T cells represent a highly dynamic system with constant homeostatic and antigen-driven proliferation, influx, and loss of T cells. Thymic activity dwindles with age and essentially ceases in the later decades of life, severely constraining the generation of new T cells. Homeostatic control mechanisms are very effective to maintain a large and diverse subset of naïve CD4 T cells for many years up to the 8 th decade of life, but eventually and abruptly fail at about the age of 75 years. In contrast, the CD8 T cell compartment is more unstable, with progressive diminution of naïve T cells and increasing loss of diversity already during mid adulthood. Vaccination strategies need to aim at developing a broad repertoire of memory T cells before the critical time period when the naïve CD4 T-cell repertoire collapses. Research efforts need to aim at understanding the homeostatic control mechanisms to ultimately expand the time period of repertoire stability.Adaptive immune responses are initiated when T cells recognize endogenous antigen on activated and mature antigen-presenting cells. Successful responses depend on the repertoire of existing T cells (Nikolich-Zugich et al., 2004). The diversity of the T-cell compartment determines whether T cells are available that recognize antigen with high avidity. The frequency of each T-cell specificity in the existing repertoire influences how fast an initial immune recognition event can be amplified to generate a sufficient number of effector cells. Consequently, the naïve T-cell repertoire is highly diverse, providing the ability to recognize the universe of exogenous and potentially dangerous antigens. In contrast, the memory T-cell repertoire is selected by previous antigen exposure. Each memory T cell clone is present in larger frequency, guaranteeing a more rapid response upon re-exposure to the same antigen. Homeostatic regulation is important not only to control the size of the T-cell compartment, but also the composition of naïve and memory T cells, as well as the diversity of each T-cell compartment (Goldrath and Bevan, 1999a).
T cell homeostasis and ageThe homeostatic control mechanisms have to deal with exogenous and endogenous challenges (Freitas and Rocha, 2000;Jameson, 2002). The T-cell compartment is a highly dynamic T-cell reservoir with sometimes conflicting kinetics of singular components that compete for space. The most evident example is the clonal expansion that occurs after naïve or memory T cells encounter antigen. This clonal expansion is dramatic and has been estimated to include 10 to 15 population doublings followed by equally rapid clonal contraction with a majority of *Corresponding author. Mailing address: Lowance Center for Human Immunology, Emory University School of Medicine, 101 Woodruff Circle #1003, Atlanta, GA 30322. Phone: (404) 727-7310. Fax: (404) 727-7371. E-mail: E-mail: jgoronz@emory.edu.. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As...