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

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.

Human T Cell Development, Localization, and Function throughout Life

“…Adults who underwent neonatal thymectomy (many now in their third-to-fourth decade of life) do not experience increased incidence of infections (Mancebo et al, 2008; Wells et al, 1998), and remain healthy despite having more extensive declines in naïve T cell frequencies with age compared to control individuals (Prelog et al, 2009; van den Broek et al, 2016). Moreover, neonatally thymectomized adults do not have increased incidences of autoimmunity or allergy compared to aged-matched controls (Silva et al, 2017), consistent with their maintenance of normal blood Treg cell frequencies and numbers (Silva et al, 2016). However, infants born with a congenital defect in Treg cell development (based on deletion or mutation of the Foxp3 transcription factor) present with Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked (IPEX) syndrome manifested by systemic autoimmunity and multi-organ infiltrates (Bennett et al, 2001).…”

Interruption of thymic activity in adults improves responses to tumor immunotherapy

“…Upon added stress on the Treg compartment, such as during immune check-point inhibitor therapy, the inability of the thymus to replenish this cell pool results in unbalanced immune responses, including enhanced anti-tumor immunity. This model highlights the robustness of the immune system, explains the overall efficient immune responses (29) and mild increase in auto-reactive Ab (38) presented by humans submitted to surgical thymectomy, and argues that higher incidence of tumors with age cannot be solely attributed to thymic output decline. Further refinement of this minutes after which a Percol gradient (Sigma) was used to isolate lymphocytes.…”

Recurrent oral ulcerations following heart transplant in a pediatric patient: A diagnostic dilemma

“…26,27 It remains to be seen whether thymectomy produces a clinically significant alteration in the ratio of different T-cell populations because of extrathymic Treg development. 26,28 This case highlights the importance of thinking broadly about the differential diagnosis of non-specific symptoms, such as oral ulcers, in the post-SOT population. To our knowledge, this is the first description of a patient to be diagnosed with Behçet's disease post-SOT.…”

“…Increased numbers of autoantibodies have been identified in thymectomized children, compared to healthy controls . It remains to be seen whether thymectomy produces a clinically significant alteration in the ratio of different T‐cell populations because of extrathymic Treg development …”