Evidence of premature immune aging in patients thymectomized during early childhood
Delphine Sauce, … , Daniel Sidi, Victor Appay
Delphine Sauce, … , Daniel Sidi, Victor Appay
Published September 21, 2009
Citation Information: J Clin Invest. 2009;119(10):3070-3078. https://doi.org/10.1172/JCI39269.
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Research Article

Evidence of premature immune aging in patients thymectomized during early childhood

Abstract

While the thymus is known to be essential for the initial production of T cells during early life, its contribution to immune development remains a matter of debate. In fact, during cardiac surgery in newborns, the thymus is completely resected to enable better access to the heart to correct congenital heart defects, suggesting that it may be dispensable during childhood and adulthood. Here, we show that young adults thymectomized during early childhood exhibit an altered T cell compartment. Specifically, absolute CD4+ and CD8+ T cell counts were decreased, and these T cell populations showed substantial loss of naive cells and accumulation of oligoclonal memory cells. A subgroup of these young patients (22 years old) exhibited a particularly altered T cell profile that is usually seen in elderly individuals (more than 75 years old). This condition was directly related to CMV infection and the induction of strong CMV-specific T cell responses, which may exhaust the naive T cell pool in the absence of adequate T cell renewal from the thymus. Together, these marked immunological alterations are reminiscent of the immune risk phenotype, which is defined by a cluster of immune markers predictive of increased mortality in the elderly. Overall, our data highlight the importance of the thymus in maintaining the integrity of T cell immunity during adult life.

Authors

Delphine Sauce, Martin Larsen, Solène Fastenackels, Anne Duperrier, Michael Keller, Beatrix Grubeck-Loebenstein, Christophe Ferrand, Patrice Debré, Daniel Sidi, Victor Appay

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Figure 4

Phenotypic and functional assessment of virus-specific CD8+ T cells in YATECs.

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Phenotypic and functional assessment of virus-specific CD8+ T cells in Y...
(A) Representative staining of CD27 on HLA-A11 EBV EBNA-3B AK10–specific CD8+ T cells identified in 1 YATEC and 1 control subject. Percentages of CD27– or CD27+ cells within tetramer-positive populations are shown. (B) Expression of the differentiation markers CD27 or CD57 on EBV- or CMV-specific CD8+ T cells, identified using tetramers in YATECs or control individuals. Horizontal bars indicate the median. (C) Representative example of simultaneous multifunctional assessment of B8-FL9 EBV–specific CD8+ T cells from a YATEC patient. Cells were stimulated overnight in the presence of cognate peptide prior to intracellular staining and analysis using 9-color flow cytometry. Percentages of cells in the different quadrants are shown. Plots are gated on CD3+CD8+ T cells and tetramer-positive T cells, respectively. (D) Polyfunctional profiling of EBV-specific CD8+ T cell populations from YATECs (n = 8) or controls (n = 10) upon stimulation with their cognate peptide. For simplicity, percentages of cells are grouped according to the number of functions (from CD107a or CD40L, IFN-γ, TNF-α, IL-2, and MIP-1β) elicited in response to antigen encounter. Individual segments of the pie charts represent the proportions of cells within each total population that exhibited the number of functions indicated. (E) Polyfunctional profiling of CMV-specific CD8+ or CD4+ T cell populations from CMV-seropositive YATECs (n = 15) or CMV-seropositive controls (n = 15) upon stimulation with pp65 and IE1 overlapping peptides.