Abstract
The thymus begins involution in childhood and historically it was thought to be nonfunctional by adulthood, thus presenting no contraindication to the routine practice of thymectomy during cardiothoracic surgery. More recent data suggest, however, that the thymus remains active into adulthood and is responsible for the low-level production of normal T cells. We hypothesize, therefore, that incidental thymectomy during cardiothoracic surgery in infancy causes long-term changes in the cellular immune system. To investigate this hypothesis, we quantified peripheral T-cell subsets and T-cell recombination excision circles in children with congenital heart disease to measure the impact of cardiothoracic surgical procedures and thymectomy performed during a period of immunologic development. We found that cardiothoracic surgical procedures, especially if they include thymectomy, impair T-cell production and produce long-term decreases in total lymphocyte count and CD4+ and CD8+ T-cell subsets, suggesting that long-term maintenance of lymphocyte populations is disturbed.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
Abbreviations
- MG:
-
myasthenia gravis
- PBMC:
-
peripheral blood mononuclear cells
- RTE:
-
recent thymic emigrants
- TREC:
-
T cell receptor recombination excision circles
References
Barrett DJ, Ammann AJ, Wara DW, Cowan MJ, Fisher TJ, Stiehm ER 1981 Clinical and immunologic spectrum of the DiGeorge syndrome. J Clin Lab Immunol 6: 1–6
Jawad AF, McDonald-McGinn DM, Zackai E, Sullivan KE 2001 Immunologic features of chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). J Pediatr 139: 715–723
Piliero LM, Sanford AN, McDonald-McGinn DM, Zackai EH, Sullivan KE 2004 T-cell homeostasis in humans with thymic hypoplasia due to chromosome 22q11.2 deletion syndrome. Blood 103: 1020–1025
Ramos SB, Garcia AB, Viana SR, Voltarelli JC, Falcao RP 1996 Phenotypic and functional evaluation of natural killer cells in thymectomized children. Clin Immunol Immunopathol 81: 277–281
Wells WJ, Parkman R, Smogorzewska E, Barr M 1998 Neonatal thymectomy: does it effect immune function?. J Thorac Cardiovasc Surg 115: 1041–1046
Eysteinsdottir JH, Freysdottir J, Haraldsson A, Stefansdottir J, Skaftadottir I, Helgason H, Ogmundsdottir HM 2004 The influence of partial or total thymectomy during open heart surgery in infants on the immune function later in life. Clin Exp Immunol 136: 349–355
Gennery AR, Barge D, Spickett GP, Cant AJ 2001 Lymphocyte subset populations in children with polysaccharide antibody deficiency following cardiac transplantation. J Clin Immunol 21: 37–42
De Rosa SC, Herzenberg LA, Herzenberg LA, Roederer M 2001 11-color, 13-parameter flow cytometry: identification of human naïve T cells by phenotype, function, and T-cell receptor diversity. Nat Med 7: 245–248
Douek DC, Vescio RA, Betts MR, Brenchley JM, Hill BJ, Zhang L, Berenson JR, Collins RH, Koup RA 2000 Assessment of thymic output in adults after haematopoietic stem-cell transplantation and prediction of T-cell reconstitution. Lancet 355: 1875–1881
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 1998 Changes in thymic function with age and during the treatment of HIV infection. Nature 396: 690–695
Kong F, Chen CH, Cooper MD 1998 Thymic function can be accurately monitored by the level of recent T cell emigrants in the circulation. Immunity 8: 97–104
Steffens CM, Al-Harthi L, Shott S, Yogev R, Landay A 2000 Evaluation of thymopoiesis using T cell receptor excision circles (TRECs): differential correlation between adult and pediatric TRECs and naïve phenotypes. Clin Immunol 97: 95–101
Ye P, Kirschner DE 2002 Reevaluation of T cell receptor excision circles as a measure of human recent thymic emigrants. J Immunol 169: 4968–4979
Haynes BF, Hale LP, Weinhold KJ, Patel DD, Liao H, Bressler PB, Jones DM, Demarest JF, Gebhard-Mitchell K, Haase AT, Bartlett JA 1999 Analysis of the adult thymus in reconstitution of T lymphocytes in HIV-1 infection. J Clin Invest 103: 453–460
Haynes BF, Markert ML, Sempowski GD, Patel DD, Hale LP 2000 The role of the thymus in immune reconstitution in aging, bone marrow, transplantation, and HIV-1 infection. Annu Rev Immunol 18: 529–560
Heitger A, Neu N, Kern H, Panzer-Grumayer ER, Greinix H, Nachbaur D, Niederwieser D, Fink FM 1997 Essential role of the thymus to reconstitute naive (CD45RA+) T-helper cells after human allogeneic bone marrow transplantation. Blood 90: 850–857
Mackall CL, Hakim FT, Gress RE 1997 T-cell regeneration: all repertoires are not created equal. Immunol Today 18: 245–251
Zhang L, Lewin SR, Markowitz M, Lin HH, Skulsky E, Karanicolas R, He Y, Jin X, Tuttleton S, Vesanen M, Spiegel H, Kost R, van Lunzen J, Stellbrink H, Wolinsky S, Borokowsky W, Palumbo P, Kostrikis LG, Ho DD 1999 Measuring recent thymic emigrants in blood of normal and HIV-1 infected individuals before and after effective therapy. J Exp Med 190: 725–732
Pham T, Belzer M, Church JA, Kitchen C, Wilson CM, Douglas SD, Geng Y, Silva M, Mitchell RM, Krogstad P 2003 Assessment of thymic activity in human immunodeficiency virus-negative and -positive adolescents by real-time PCR quantitation of T-cell receptor rearrangement excision circles. Clin Diag Lab Immunol 10: 323–328
Vigano A, Vella S, Saresella M, Vanzulli A, Bricalli D, DiFabio S, Ferrante P, Andreotti M, Pirillo M, Dally LG, Clerici M, Principi N 2000 Early immune reconstitution after potent antiretroviral therapy in HIV- infected children correlates with the increase in thymus volume. AIDS 14: 251–261
Storek J, Douek DC, Keesey JC, Boehmer L, Storer B, Maloney DG 2003 Low T cell receptor excision circle levels in patients thymectomized 25–54 years ago. Immunol Lett 89: 91–92
Comans-Bitter WM, deGroot R, van den Beemd R, Hop WC, Groeneveld K, Hooijkaas H, van Dongen JJ 1997 Immunophenotyping of blood lymphocytes in childhood. Reference values for lymphocyte subpopulations. J Pediatr 130: 388–393
Jamieson BD, Douek DC, Killian S, Hultin LE, Scripture-Adams DD, Giorgi JV, Marelli D, Koup RA, Zack JA 1999 Generation of functional thymocytes in the human adult. Immunity 10: 569–575
Poulin JF, Viswanathan MN, Harris JM, Komanduri KV, Wieder E, Ringuette N, Jenkins M, McCune JM, Sekaly RP 1999 Direct evidence for thymic function in adult humans. J Exp Med 190: 479–486
Fry TJ, Mackall CL 2002 Current concepts of thymic ageing. Springer Semin Immunopathol 24: 7–22
Sempowski GD, Thomasch JR, Gooding ME, Hale LP, Edwards LJ, Ciafaloni E, Sanders DB, Massey JM, Douek DC, Koup RA, Haynes BF 2001 Effect of thymectomy on human peripheral blood T cell pools in myasthenia gravis. J Immunol 166: 2808–2817
Effros RB, Globerson A 2002 Hematopoietic cells and replicative senescence. Exp Gerontol 37: 191–196
Napolitano LA, Grant RM, Deeks SG, Schmidt D, DeRosa SC, Herzenberg LA, Herndier BG, Andersson J, McCune JM 2001 Increased production of IL-7 accompanies HIV-1-mediated T-cell depletion: implications for T-cell homeostasis. Nat Med 7: 73–79
Author information
Authors and Affiliations
Corresponding author
Additional information
Supported by a Research Fellowship Award from the American Academy of Pediatrics to N.H. and the Laubisch Foundation. The authors would like to acknowledge Mr. Gerald Oppenheim for a seed grant that supported this research. P.K. is an Elizabeth Glaser Scientist of the Pediatric AIDS Foundation. Flow cytometry was performed in the UCLA Jonsson Comprehensive Cancer Center and Center for AIDS Research Flow Cytometry Core Facility that is supported by National Institutes of Health awards CA-16042 and AI-28697, by the Jonsson Cancer Center, the UCLA AIDS Institute, and the UCLA School of Medicine.
Rights and permissions
About this article
Cite this article
Halnon, N., Jamieson, B., Plunkett, M. et al. Thymic Function and Impaired Maintenance of Peripheral T Cell Populations in Children with Congenital Heart Disease and Surgical Thymectomy. Pediatr Res 57, 42–48 (2005). https://doi.org/10.1203/01.PDR.0000147735.19342.DE
Received:
Accepted:
Issue date:
DOI: https://doi.org/10.1203/01.PDR.0000147735.19342.DE
This article is cited by
-
Thymic Atrophy and Immune Dysregulation in Infants with Complex Congenital Heart Disease
Journal of Clinical Immunology (2024)
-
Immunity and inflammation: the neglected key players in congenital heart disease?
Heart Failure Reviews (2022)
-
Neutrophil and T Cell Functions in Patients with Congenital Heart Diseases: A Review
Pediatric Cardiology (2021)
-
The Case for Cardiac Xenotransplantation in Neonates: Is Now the Time to Reconsider Xenotransplantation for Hypoplastic Left Heart Syndrome?
Pediatric Cardiology (2019)
-
Efforts of the human immune system to maintain the peripheral CD8+ T cell compartment after childhood thymectomy
Immunity & Ageing (2016)
