A fundamental feature of mammalian adaptive immunity is the highly diverse pool of antigen receptors found on lymphocytes. The T-cell receptor and the surface immunoglobulin on B cells facilitate the recognition of foreign structures found on tumors and pathogens that have overwhelmed the defenses of the innate immune system. Because pathogen encounters and neoplasic transformations are inherently unpredictable, an immense lymphocyte receptor repertoire is required to meet all of the possible challenges an organism will face. In young humans, the daily production of naïve B cells from the bone marrow and T cells from the thymus steadily injects the lymphocyte pool with new antigen receptors. Unfortunately, as humans age functional thymic tissue gradually involutes and is replaced by fat. In parallel, the daily production of new naïve T cells declines such that no meaningful thymic T-cell production occurs after the age of fifty. Thus, the T-cell repertoire of an adult human must be maintained for decades in the absence of a replenishing source. Although homeostatic mechanisms are remarkably successful at maintaining the T-cell repertoire for many years, obvious changes begin to emerge with advanced age. Most strikingly, the naïve CD4 T cells that remain after the age of 65 undergo a sudden and dramatic collapse of T-cell receptor diversity. Naïve CD8 T cells may experience an earlier and more gradual diversity loss, although direct evidence for this is not yet available. A steadily expanding memory population maintains total T-cell numbers despite the decline in naïve T cells. Among these memory cells, an increasing percentage acquires a terminally differentiated phenotype characterized by abnormal expression of regulatory receptors and resistance to apoptosis. Oligoclonal populations accumulate after a lifetime of repeated challenges such as chronic infections, leading to a contracted memory repertoire. Although the consequences of repertoire contraction are not yet known, this phenomenon may have important implications for the health of the ever growing elderly population.
|Original language||English (US)|
|Title of host publication||Handbook on Immunosenescence|
|Subtitle of host publication||Basic Understanding and Clinical Applications|
|Number of pages||26|
|State||Published - 2009|
ASJC Scopus subject areas