The role of the thymus in immunosenescence: lessons from the study of thymectomized individuals

Victor Appay, Delphine Sauce, Martina Prelog, Victor Appay, Delphine Sauce, Martina Prelog

Abstract

The thymus is the major site of T cell production and a key organ of the immune system. Its natural involution during the course of life has cast doubts as to its importance for the integrity of our immunity in adulthood. We provide here an overview of the recent works focusing on the immunological evaluation of subjects thymectomized during early childhood due to cardiac surgery of congenital heart defects. These studies represent new advances in our appreciation of the role of the thymus in humans and more generally in our understanding of the development of immunosenescence.

Conflict of interest statement

The authors of this manuscript have no conflict of interest to declare.

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

References

    1. Douek DC, McFarland RD, Keiser PH, Gage EA, Massey JM, Haynes BF, Polis MA, Haase AT, Feinberg MB, Sullivan JL, Jamieson BD, Zack JA, Picker LJ, Koup RA. Changes in thymic function with age and during the treatment of HIV infection. Nature. 1998;396:690–695.
    1. Gruver AL, Hudson LL, Sempowski GD. Immunosenescence of ageing. J Pathol. 2007;211:144–156.
    1. Rubinstein A, Pelet B, Schweizer V. Immunological decay in thymectomized infants. Helv Paediatr Acta. 1976;30:425–433.
    1. Moretta L, Mingari MC, Webb SR, Pearl ER, Lydyard PM, Grossi CE, Lawton AR, Cooper MD. Imbalances in T cell subpopulations associated with immunodeficiency and autoimmune syndromes. Eur J Immunol. 1977;7:696–700.
    1. Miller JF. Immunological function of the thymus. Lancet. 1961;2:748–749.
    1. Marchant A, Appay V, Van der Sande M, Dulphy N, Liesnard C, Kidd M, Kaye S, Ojuola O, Gillespie G, Vargas Cuero A, Cerundolo V. Mature CD8+ T lymphocyte response to viral infection during foetal life. J Clin Invest. 2003;11:1747–1755.
    1. Adkins B, Leclerc C, Marshall-Clarke S. Neonatal adaptive immunity comes of age. Nat Rev Immunol. 2004;4:553–564.
    1. Wells WJ, Parkman R, Smogorzewska E, Barr M. Neonatal thymectomy: does it affect immune function. J Thorac Cardiovasc Surg. 1998;115:1041–1046.
    1. Eysteinsdottir JH, Freysdottir J, Haraldsson A, Stefansdottir J, Skaftadottir I, Helgason H, Ogmundsdottir HM. The influence of partial or total thymectomy during open heart surgery in infants on the immune function later in life. Clin Exp Immunol. 2004;136:349–355.
    1. Madhok AB, Chandrasekran A, Parnell V, Gandhi M, Chowdhury D, Pahwa S. Levels of recent thymic emigrant cells decrease in children undergoing partial thymectomy during cardiac surgery. Clin Diagn Lab Immunol. 2005;12:563–565.
    1. Torfadottir H, Freysdottir J, Skaftadottir I, Haraldsson A, Sigfusson G, Ogmundsdottir HM. Evidence for extrathymic T cell maturation after thymectomy in infancy. Clin Exp Immunol. 2006;145:407–412.
    1. Ogle BM, West LJ, Driscoll DJ, Strome SE, Razonable RR, Paya CV Cascalho M, Platt JL. Effacing of the T cell compartment by cardiac transplantation in infancy. J Immunol. 2006;176:1962–1967.
    1. Prelog M, Keller M, Geiger R, Brandstatter A, Wurzner R, Schweigmann U, Zlamy M, Zimmerhackl LB, Grubeck-Loebenstein B. Thymectomy in early childhood: Significant alterations of the CD4(+)CD45RA(+)CD62L(+) T cell compartment in later life. Clin Immunol. 2008;130:23–32.
    1. Sauce D, Larsen M, Fastenackels S, Duperrier A, Keller M, Grubeck-Loebenstein B, Ferrand C, Debre P, Sidi D. and Appay V. Evidence of premature immune aging in patients thymectomized during early childhood. J Clin Invest. 2009;119:3070–3078.
    1. Pawelec G, Koch S, Franceschi C, Wikby A. Human immunosenescence: does it have an infectious component. Ann N Y Acad Sci. 2006;1067:56–65.
    1. Sylwester AW, Mitchell BL, Edgar JB, Taormina C, Pelte C, Ruchti F, Sleath PR, Grabstein KH, Hosken NA, Kern F, Nelson JA, Picker LJ. Broadly targeted human cytomegalovirus-specific CD4+ and CD8+ T cells dominate the memory compartments of exposed subjects. J Exp Med. 2005;202:673–685.
    1. Kuijpers TW, Vossen MT, Gent MR, Davin JC, Roos MT, Wertheim-van Dillen PM, Weel JF, Baars PA, van Lier RA. Frequencies of circulating cytolytic, CD45RA+CD27-, CD8+ T lymphocytes depend on infection with CMV. J Immunol. 2003;170:4342–4348.
    1. Snyder CM, Cho KS, Bonnett EL, van Dommelen S, Shellam GR, Hill AB. Memory inflation during chronic viral infection is maintained by continuous production of short-lived, functional T cells. Immunity. 2008;29:650–659.
    1. Grubeck-Loebenstein B, Wick G. The aging of the immune system. Adv Immunol. 2002;80:243–284.
    1. Prelog M, Wilk C, Keller M, Karall T, Orth D, Geiger R, Walder G, Laufer G, Cottogni M, Zimmerhackl Lothar B, Stein J, Grubeck-Loebenstein B, Wuerzner R. Diminished response to tick-borne encephalitis vaccination in thymectomized children. Vaccine. 2008;26:595–600.
    1. Hainz U, Jenewein B, Asch E, Pfeiffer KP, Berger P, Grubeck-Loebenstein B. Insufficient protection for healthy elderly adults by tetanus and TBE vaccines. Vaccine. 2005;23:3232–3235.
    1. Ferguson FG, Wikby A, Maxson P, Olsson J, Johansson B. Immune parameters in a longitudinal study of a very old population of Swedish people: a comparison between survivors and nonsurvivors. J Gerontol A Biol Sci Med Sci. 1995;50:B378–382.
    1. Wikby A, Maxson P, Olsson J, Johansson B, Ferguson FG. Changes in CD8 and CD4 lymphocyte subsets, T cell proliferation responses and non-survival in the very old: the Swedish longitudinal OCTO-immune study. Mech Ageing Dev. 1998;102:187–198.

Source: PubMed

3
Sottoscrivi