Abstract
IntroductionA tight balance between regulatory CD4+Foxp3+ (Treg) and conventional CD4+Foxp3− (Tconv) T cell subsets in the peripheral compartment, maintained stable throughout most of lifetime, is essential for preserving self‐tolerance along with efficient immune responses. An excess of Treg cells, described for aged individuals, may critically contribute to their reported immunodeficiency. In this work, we investigated if quantitative changes in thymus emigration may alter the Treg/Tconv homeostasis regardless of the aging status of the peripheral compartment.MethodsWe used two different protocols to modify the rate of thymus emigration: thymectomy of adult young (4–6 weeks old) mice and grafting of young thymus onto aged (18 months old) hosts. Additionally, lymphoid cells from young and aged B6 mice were intravenously transferred to B6.RAG2−/− mice. Alterations in Treg and Tconv peripheral frequencies following these protocols were investigated after 30 days by flow cytometry.ResultsThymectomized young mice presented a progressive increase in the Treg cell frequency, while the grafting of a functional thymus in aged mice restored the young‐like physiological Treg/Tconv proportion. Strikingly, T cells derived from young or aged splenocytes colonized the lymphopenic periphery of RAG−/− hosts to the same extent, giving rise to similarly elevated Treg cell levels irrespective of the age of the donor population. In the absence of thymus output, the Treg subset seems to survive longer, as confirmed by their lower proportion of Annexin‐V+ cells.ConclusionsOur data suggest that the thymus‐emigrating population, harboring an adequate proportion of Treg/Tconv lymphocytes, may be essential to keep the Treg cell balance, independently of age‐related shifts intrinsic to the peripheral environment or to the T cell biology.
Highlights
A tight balance between regulatory CD4þFoxp3þ (Treg) and conventional CD4þFoxp3À (Tconv) T cell subsets in the peripheral compartment, Methods: We used two different protocols to modify the rate of thymus
Our data suggest that the thymus-emigrating population, harboring an adequate proportion of Treg/Tconv lymphocytes, may be essential to keep the
CD4þFoxp3þ regulatory T (Treg) cells, kept as 5–10% of the peripheral T lymphocytes during most adult life, comprises two different major subsets: the natural thymicderived Treg cells, selected through high-affinity interactions with self-peptides presented by the thymic stroma and usually characterized by Helios and neuropilin-1 (Nrp-1) expression; and the peripherally induced regulatory T cells, derived from na€ıve Foxp3-negative lymphocytes after TCR stimulation in the presence of adequate cytokine stimulation [4,5,6,7,8,9]
Summary
A tight balance between regulatory CD4þFoxp3þ (Treg) and conventional CD4þFoxp3À (Tconv) T cell subsets in the peripheral compartment, Methods: We used two different protocols to modify the rate of thymus. CD4þFoxp3þ regulatory T (Treg) cells, kept as 5–10% of the peripheral T lymphocytes during most adult life, comprises two different major subsets: the natural thymicderived Treg cells (tTreg), selected through high-affinity interactions with self-peptides presented by the thymic stroma and usually characterized by Helios and neuropilin-1 (Nrp-1) expression; and the peripherally induced regulatory T cells (pTreg), derived from na€ıve Foxp3-negative lymphocytes after TCR stimulation in the presence of adequate cytokine stimulation [4,5,6,7,8,9]. Each of these subsets encompasses a unique and complementary TCR repertoire, both necessary to control several autoimmune pathologies [10,11,12]
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