The Involution of the Ageing Human Thymic Epithelium is Independent of Puberty

Steinmann, Gerhard; Klaus, Beate; Müller-Hermelink, H. K.

doi:10.1111/j.1365-3083.1985.tb01916.x

Cited by 407 publications

(358 citation statements)

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“…Thymic epithelial space, which is the best biological correlate of functionally active tissues, declines from about 7 cm 3 in the young adult to about 1 cm 3 in the 55 to 65 year old. Recent studies have shown islands of functional tissue in the thymus of the elderly (Haynes et al, 2000;Steinmann et al, 1985;Steinmann, 1986); however, it is uncertain whether production of new thymocytes in these residual tissues is of quantitative importance.In the absence of phenotypic markers specific for thymic emigrants, most studies of thymic output have relied on measuring T-cell receptor excision circles (TREC) (Douek et al, 1998;Kong et al, 1999). These signal-joint TRECs are formed during T-cell receptor (TCR)-α-chain rearrangement, when a substantial portion of the TCR δ locus is excised.…”

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confidence: 99%

Aging and T-cell diversity☆

Goronzy

Lee

Weyand

2007

Experimental Gerontology

243

187

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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...

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confidence: 99%

Aging and T-cell diversity☆

Goronzy

Lee

Weyand

2007

Experimental Gerontology

243

187

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“…It is now appreciated that the true TES begins to involute beginning at the first year of life, whereas the PVS involutes at a different pace, increasing in size from the age of 1 yr until young adulthood, and then decreasing in size thereafter. Thus, the human TES reaches its maximum size at age 1, whereas the lymphoid volume of the PVS is only a potential space at birth, peaks in volume between ages 10 and 25, and decreases in volume thereafter (36)(37)(38). It is also important to note that the human thymus, in contrast to the mouse thymus, does not lose its volume during aging (36).…”

Section: The Thymus In Agingmentioning

confidence: 99%

“…To appreciate the changes that occur in thymus morphology in aging, MG, and in HIV infection, it is important to understand the (31)(32)(33)(34)(35)(36)(37). As will be discussed below, the latter two postulates are the most likely to be the case, depending on the age of the thymus and the clinical setting.…”

Section: The True Thymic Epithelial Space and The Thymic Perivascularmentioning

confidence: 99%

“…Confusion on this point arose because early investigators did not appreciate the presence of the PVS in addition to the TES in human thymus. Steinmann and colleagues have clarified this point, and in 1986 summarized their work and the work of others (36,37). It is now appreciated that the true TES begins to involute beginning at the first year of life, whereas the PVS involutes at a different pace, increasing in size from the age of 1 yr until young adulthood, and then decreasing in size thereafter.…”

Section: The Thymus In Agingmentioning

confidence: 99%

“…Thus, the human TES reaches its maximum size at age 1, whereas the lymphoid volume of the PVS is only a potential space at birth, peaks in volume between ages 10 and 25, and decreases in volume thereafter (36)(37)(38). It is also important to note that the human thymus, in contrast to the mouse thymus, does not lose its volume during aging (36). Rather, the human thymus retains its size and volume during life, and by processes and stimuli that are poorly understood, the TES involutes whereas the PVS lymphoid component initially increases, and then eventually decreases in volume.…”

Section: The Thymus In Agingmentioning

confidence: 99%

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The human thymus

Haynes

Hale

1998

Immunol Res

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The human thymus is a lymphoepithelial organ in which T cells develop during fetal life. After maturation and selection in the fetal thymic microenvironment, T cells emigrate to peripheral lymphoid tissues such as the spleen, gut, and lymph nodes, and establish the peripheral T cell repertoire. Although the thymus has enormous regenerative capacity during fetal development, the regenerative capacity of the human postnatal thymus decreases over time. With the advent of intensive chemotherapy regimens for a variety of cancer syndromes, and the discovery that infection with the Human Immunodeficiency Virus (HIV) leads to severe loss of CD4 + T cells, has come the need to understand the role of the human thymus in reconstitution of the immune system in adults. During a recent study of the thymus in HIV infection, we observed many CD8 + T cells in AIDS thymuses that had markers consistent with those of mature effector cytotoxic T cells usually found in peripheral immune tissues, and noted these CD8 + effector T cells were predominately located in a thymic zone termed the thymic perivascular space. This article reviews our own work on the thymus in HIV-1 infection, and discusses the work of others that, taken together, suggest that the thymus contains peripheral immune cell components not only in the setting of HIV infection, but also in myasthenia gravis, as well as throughout normal life during the process of thymus involution. Thus, the human thymus can be thought of as a chimeric organ comprised of both central and peripheral lymphoid tissues. These observations have led us to postulate that the thymic epithelial atrophy and decrease in thymopoiesis that occurs in myasthenia gravis, HIV-I infection, and thymic involution may in part derive from cytokines or other factors produced by peripheral immune cells within the thymic perivascular space.

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Evolutionary process and the ecology of human immune function

McDade

Worthman

1999

Am. J. Hum. Biol.

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Evolutionary principles inform central design features of human immune defenses and provide key insights into this complicated host defense system. This article explores the selection pressures and adaptive responses that have elaborated the immune system over the course of evolution and discusses their implications for understanding contemporary immune development and function. Special attention is given to the challenges posed by diverse, rapidly evolving pathogens and the mammalian response to these challenges. The process of lymphocyte diversity generation and subsequent clonal selection is quintessentially Darwinian: pathogens provide selection pressure that drives differential replication of host immune cell lines, resulting in changes in genetic frequencies within an individual's population of lymphocytes. The immune system also incorporates nongenetic transgenerational processes in the transfer of antibodies from mother to offspring through the placenta and breast milk. The consequences of these observations for human development, health, and the ecology of immune function are considered throughout the life cycle. Specifically, evolutionary processes provide insight into autoimmunity, thymic function, lymphocyte development, infectious disease risk, and lactation. While much work in evolutionary medicine focuses on the discordance between evolved biology and rapidly changing cultural environments, with respect to the immune system, evolutionary processes may be most revealing when applied within individuals. Am. J. Hum. Biol. 11:705–717, 1999. © 1999 Wiley‐Liss, Inc.

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The Involution of the Ageing Human Thymic Epithelium is Independent of Puberty

Cited by 407 publications

References 24 publications

Aging and T-cell diversity☆

Aging and T-cell diversity☆

The human thymus

Evolutionary process and the ecology of human immune function

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