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. 2009 Jun;31(2):87-97.
doi: 10.1007/s11357-008-9084-x. Epub 2009 Jan 31.

Thymopoiesis in elderly human is associated with systemic inflammatory status

Sara Ferrando-Martínez  1 , Jaime M Franco, Ana Hernandez, Antonio Ordoñez, Encarna Gutierrez, Antonia Abad, Manuel Leal
Affiliations

Thymopoiesis in elderly human is associated with systemic inflammatory status

Sara Ferrando-Martínez et al. Age (Dordr). 2009 Jun.

Abstract

Immunosenescence studies of age-related immune system damage focused on clinical lymphopenic situations or androgenic blockade have revealed new insights about adult human immune reconstitution. However, as far as we know, the extent of lymphopoiesis in the thymus of elderly humans remains unclear. To this effect, we have analyzed 65 adult human thymuses (from 36 to 81 years; median age 68.6 years) obtained from patients who underwent cardiac surgery. Our results show a correlation between CD4(+)CD8(+) double-positive (DP) cells and both the age (inverse) and percentage (direct) of peripheral naive T cells, indicating that the thymus is still able to affect the peripheral lymphocyte pool even in the elderly. We also found significant correlation between the degree of thymopoiesis and the inflammation markers, as shown by the inverse correlations between DP and the percentage of neutrophils and IL-6 levels and the percentage of peripheral lymphocytes. Furthermore, in a multivariate linear regression the percentage of DP and IL-7 levels, but not age, were independently associated with the percentage of neutrophils. In conclusion, the thymus maintains, even in the elderly, an active thymopoiesis that rejuvenates the peripheral naive T-cell pool. Moreover, age-related thymopoietic decay is associated with the peripheral inflammation markers.

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Figures

Fig. 1
Fig. 1
a Representative procedure for the thymic tissue surgically removal. Note the total absence of adipose tissue in the mediastinum that ensures the clear thymic tissue sample identification. b Representative histological data for the 0% DP thymic tissue samples. Photographs show an organized lymphoepithelial structure and the black arrow shows a Hassall’s corpuscle, both typical of thymic tissue samples
Fig. 2
Fig. 2
a Representative fluorescent-activated cell sorter (FACS) analysis of fresh isolated thymocytes. The plot shows the percentage of DP (CD4+CD8+) thymocytes. b Percentage of DP thymocytes among the different age groups. Black lines define the median of DP thymocytes percentage. c sjTREC numbers (directly obtained from tissue samples DNA) among the different age groups. Black lines define the median of sjTRECs/106 cells. d Relationship with the total numbers of isolated thymocytes from each thymus tissue sample. Black circles represent the direct correlation (r = 0.525, p < 0.001) with the percentage of DP thymocytes. White circles show the direct correlation (r = 0.363, p = 0.004) with the sjTREC numbers
Fig. 3
Fig. 3
a Relationship between DP thymocyte absolute numbers and the percentage of naive T cells in peripheral blood. Black circles show the correlation with CD4+ naive T cells (r = 0.318, p = 0.002, n = 61), while white circles show the correlation with CD8+ naive T cells (r = 0.363, p = 0.007, n = 56). b Relationship between the sjTREC absolute counts (obtained from DNA thymic tissue) and the percentage of naive T cells in peripheral blood. Black circles represent the correlation with the CD4+ naive T cells (r = 0.263, p = 0.046, n = 60), while white circles represent the correlation with the CD8+ naive T cells (r = 0.306, p = 0.026, n = 55)
Fig. 4
Fig. 4
a Direct correlation between the percentage of neutrophils and the IL-7 levels obtained from serum samples (r = 0.415, p = 0.002). b Relationship between serum and plasma IL-7 levels (r = 0.266, p = 0.122). This IL-7 quantification has been performed in a control group of healthy elderly. c DP thymocytes percentage medians among the three neutrophil count groups. Statistical differences were found between the normal and neutrophilic count group (p = 0.006). d IL-6 concentration among the neutrophil count groups. Statistical differences were found between the neutropenic and neutrophilic count group (p = 0.021)
Fig. 5
Fig. 5
Outline showing the relationship between the innate and adaptative immunosenescence processes
See this image and copyright information in PMC

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