Age-related changes in the cellular composition of the thymus in children

Background: T-cell development in the thymus is an extensively studied subject, mainly in mice. Nevertheless, the normal composition and cell numbers of the noninvoluted human thymus are largely unknown. Objective: We aimed to gain insight into age-related changes in different thymic subpopulations and to provide reference values for the distribution of thymocyte subsets. The composition of the normal thymus may serve as a reference for thymi in pathological conditions and may aid diagnoses of immunodeficiency diseases. Methods: Thymic lobes of 70 children (58 immunologically normal and 12 diseased), ranging in age from 8 days to 8 years old, were studied by 4-color flow-cytometric analysis. Detailed staining and gating strategies allowed us to dissect small subsets, including immature CD4-CD8- populations and thymic B, natural killer, and T-cell receptor γδ+ cells. Results: We demonstrate that distribution of thymocyte subsets changes with age and correlates with age-related fluctuations of T-lymphocyte counts in peripheral blood. Thymi of children 3 to 6 months old appear to be the most active: they have high numbers of total thymocytes, the highest percentage of double-positive cells, and large numbers of CD34 + progenitors in their thymi. Furthermore, we show that the human thymus is a site for B-cell development, because all B-cell progenitor stages that can be found in the bone marrow are also present in the thymus. Conclusion: We conclude that T-cell development in children is a dynamic process, answering the demands of a maturing and expanding immune system.

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