Evidence of premature immune aging in patients thymectomized during early childhood
Delphine Sauce, … , Daniel Sidi, Victor Appay
Delphine Sauce, … , Daniel Sidi, Victor Appay
Published October 1, 2009; First published September 21, 2009
Citation Information: J Clin Invest. 2009;119(10):3070-3078. https://doi.org/10.1172/JCI39269.
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Category: 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 6

Association between CMV-specific T cell responses and marked T cell alterations in YATECs.

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Association between CMV-specific T cell responses and marked T cell alte...
(A) CMV seropositivity among YATECs with mild (n = 17) or strong (n = 8) T cell alterations. Each circle represents one patient. The P value was calculated using the χ2 test. (B) Representative stainings for IFN-γ in CD4+ or CD8+ T cells from a CMV-seronegative YATECs or CMV-seropositive YATECs with mild or strong T cell alterations upon stimulation with Staphylococcal enterotoxin B (SEB) or pp65 overlapping peptides. Percentages of IFN-γ+ cells within CD8– or CD8+ populations are shown. (C) Percentages of CMV-specific (pp65 and IE1) T cells in YATECs with mild or profound T cell alterations. (D) Percentages of CMV-specific (pp65 and IE1) T cells in CMV-seropositive YATECs or control subjects. (E) Proportions of naive CD4+ or CD8+ T cells in YATECs or age-matched control subjects who were CMV seropositive or seronegative. (F) Correlations between percentages of pp65- or IE1-specific CD4+ or CD8+ T cells and proportions of naive CD4+ or CD8+ T cells in YATECs. In C–E, horizontal bars indicate the median. In C and F, dashed lines indicate the limit of detection. P values were calculated using the Mann-Whitney U test for group comparisons. Spearman’s rank test was used to determine correlations.