Autoimmunity and allergy control in adults submitted to complete thymectomy early in infancy.

Susana L Silva,Rémi Cheynier,Rui M M Victorino,M Conceição Pereira-Santos,Catarina Mota,Quan-Zhen Li,Ana E Sousa,Adriana Albuquerque,Andreia J Amaral

doi:10.1371/journal.pone.0180385

Abstract

The contribution of the decline in thymic activity for the emergence of autoimmunity is still debatable. Immune-competent adults submitted to complete thymectomy early in life provide a unique model to address this question. We applied here strict criteria to identify adults lacking thymic activity based on sjTREC levels, to exclude thymic rebound and/or ectopic thymuses. In agreement, they featured severe naïve CD4 T-cell depletion and contraction of T-cell receptor diversity. Notwithstanding this, there was neither increased incidence of autoimmune disease in comparison with age-matched controls nor significant changes in their IgG/IgA/IgM/IgE autoreactivity profiles, as assessed through extensive arrays. We reasoned that the observed relative preservation of the regulatory T-cell compartment, including maintenance of naïve regulatory CD4 T-cells, may contribute to limit the emergence of autoimmunity upon thymectomy. Our findings have implications in other clinical settings with impaired thymic activity, and are particularly relevant to studies of autoimmunity in ageing.

Highlights

The thymus is essential to the establishment of the “peripheral” T-cell compartment before birth and during the accelerated somatic growth of childhood, and contributes to its continuous replenishment until at least the sixth decade of life[1]
We recently reported that naïve-Tregs are preserved in adults more than 18y after complete thymectomy early in infancy, despite the marked contraction of conventional naïve CD4 T-cells[15, 16]
We found no significant differences in the prevalence of clinical manifestations in complete thymectomyzed and age-matched control individuals (Table 1)

Summary

Introduction

The thymus is essential to the establishment of the “peripheral” T-cell compartment before birth and during the accelerated somatic growth of childhood, and contributes to its continuous replenishment until at least the sixth decade of life[1]. Thymus removal early in infancy during corrective cardiac surgery is, associated with marked contraction of the naïve T-cell subset, as well as with the presence of markers of premature immune senescence, as a result of homeostatic naïve T-cell proliferation/differentiation[1, 2]. This is thought to occur mainly in response to self and environmental antigens[2], raising the question whether early.

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Conclusion