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Aim: This nationwide study evaluated the clinical impact that an early thymectomy, during congenital heart defect (CHD) surgery, had on the health of children and adolescents. Methods: The subjects were patients aged 1–15 years who had undergone CHD surgery at the University Children's Hospital, Helsinki, where all CHD surgery in Finland is carried out, from 2006 to 2018. The parents or the cases and population‐based controls, matched for sex, age and hospital district, completed electronic questionnaires. We excluded those with low birth weights or a known immunodeficiency. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) were calculated for prespecified outcomes. Results: We received responses relating to 260/450 (58%) cases and 1403/4500 (31%) controls and excluded 73 cases with persistent cardiac or respiratory complaints after surgery. The CHD group reported more recurrent hospitalisations due to infections (aOR 6.3, 95% CI 3.0–13) than the controls and more pneumonia episodes (aOR 3.5, 95% CI 2.1–5.6), asthma (aOR 2.5, 95% CI 1.5–4.1) and wheezing (aOR 2.1, 95% CI 1.5–2.9). Conclusion: Hospitalisation due to infections, pneumonia, wheezing and asthma was more common in children after a thymectomy due to open‐heart surgery than population‐based controls, underlining the importance of immunological follow‐ups. [ABSTRACT FROM AUTHOR]

The thymus gland aids in the maturation of the immune system. An overactive or malfunctioning thymus gland, as seen in thymomas, can lead to disrupted immune systems. Thymectomy, the usual treatment, can paradoxically lead to further derangements in the immune system, leading to new autoimmune disorders. Most of these reported disorders are rheumatological. Except preclinical studies, there are no reported cases of autoimmune diabetes post-thymectomy. A 25-year-old woman who had malignant thymoma underwent chemotherapy, followed by thymectomy and radiotherapy. She developed autoimmune diabetes mellitus (AID) approximately 1 year post-thymectomy, evident from raised glycated hemoglobin, anti-glutamic acid decarboxylase (GAD) antibodies, ineffectiveness of oral glucose-lowering agents, and positive response to insulin. AID can occur after thymectomy, as evidenced by animal studies and this case report. Whether these patients would have long-term outcomes and control of diabetes differently than classic type 1 diabetes mellitus (T1D) is uncertain. Further research is needed to prove causality between thymectomy and diabetes. [ABSTRACT FROM AUTHOR]

The processes regulating peripheral naive T-cell numbers and clonal diversity remain poorly understood. Conceptually, homeostatic mechanisms must fall into the broad categories of neutral (simple random birth–death models), competition (regulation of cell numbers through quorum-sensing, perhaps via limiting shared resources), adaptation (involving cell-intrinsic changes in homeostatic fitness, defined as net growth rate over time), or selection (involving the loss or outgrowth of cell populations deriving from intercellular variation in fitness). There may also be stably maintained heterogeneity within the naive T-cell pool. To distinguish between these mechanisms, we confront very general models of these processes with an array of experimental data, both new and published. While reduced competition for homeostatic stimuli may impact cell survival or proliferation in neonates or under moderate to severe lymphopenia, we show that the only mechanism capable of explaining multiple, independent experimental studies of naive CD4+ and CD8+ T-cell homeostasis in mice from young adulthood into old age is one of adaptation, in which cells act independently and accrue a survival or proliferative advantage continuously with their post-thymic age. However, aged naive T cells may also be functionally impaired, and so the accumulation of older cells via ‘conditioning through experience’ may contribute to reduced immune responsiveness in the elderly. [ABSTRACT FROM AUTHOR]

The thymus plays an important role in the development of the immune cell pool; it serves as the primary location for T-lymphocyte maturation. Early cardiac surgical interventions for congenital heart defects are necessarily associated with thymectomy, i.e. the partial or complete removal of the thymus. A newborn infant already has a functioning thymus and developed cells of the immune system. However, thymectomy eliminates the primary location where T cells differentiate and mature. This study summarizes the current knowledge of the cellular disturbances and potential clinical consequences associated with performing thymectomy in children treated surgically for congenital heart defects. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The thymus is responsible for the maturation of lymphoid precursors into T cells, and is necessary to establish the T cell pool during prenatal and early postnatal life in humans. With the years, it undergoes a natural shrinking process, referred to as involution, suspected to be central in the decline of immune competence with aging, or immunosenescence. Here, we review the recent studies focusing on the immunological consequences of abnormal thymic development and thymectomy shortly after birth. These works highlight the importance of the thymic function in preserving immune efficacy throughout life, and provide insights into the development of immune aging. [ABSTRACT FROM AUTHOR]

The effect of route of administration of contact sensitizers on the induction of antigenic competition between dinitrofluorobenzene (DNFB) and picryl chloride (PCI) and between oxazolone (Ox) and PCl was investigated. Antigenic competition (depressed contact sensitivity to PCl) was induced not only by painting with DNFB but also by the administration of DNFB via various routes, such as intravenous (i.v.), oral or subcutaneous routes. Antigenic competition was abolished by the treatment with cyclophosphamide (CY)4 days after i.v. injection of competing DNFB or Ox, and also by thymectomy 6 weeks prior to the injection of DNFB. These results suggest that thymus-derived suppressor cells may be involved in the antigenic competition induced by the i.v. injection of DNFB. Primary contact sensitivity (CS) was induced by painting of DNFB or Ox and also by i.v. injection of Ox. Although an i.v. injection of DNFB into normal mice did not induce CS, it induced a strong CS in the mice pretreated with CY 2 days prior to the injection of DNFB. Examination on the effect of dose of contact sensitizers on the induction of antigenic competition, primary CS and tolerance by painting or by i.v. injection of DNFB or Ox showed that the degree of antigenic competition has a closer relationship with CS, than with unresponsiveness. [ABSTRACT FROM AUTHOR]

In mice thymectomized as newborns, thymectomized as adults and irradiated, and in nude mice with congenital absence of the thymus, there is a marked reduction in the number of θ-bearing lymphocytes in the lymph nodes and spleen. This suggests that θ is present on those lymphocytes which are thymus-derived. Using 51Cr and dye exclusion cytotoxic testing, approximately 65-85 per cent of lymph node and thoracic duct lymphocytes and 30-50 per cent of spleen lymphocytes were found to have θ on their surface. [ABSTRACT FROM AUTHOR]

Thymus was labelled in vivo by injecting newborn C3H/Bi mice with three or four doses of 2 μc of [3H]thymidine. The labelled thymus was grafted into the kidney capsule of 22-25-day-old intact and thymectomized syngeneic recipients which were killed 18, 41 or 42 days later. The grafts and lymphoid tissue were sectioned and examined by autoradiography after exposure times of up to 26 weeks. Small and medium labelled lymphocytes were seen in the thymus-dependent areas of the lymph nodes and spleen of all recipients provided the sections were exposed for a sufficiently long period. More labelled cells were seen in recipients killed at 18 days than at 41 or 42 days after grafting. It was concluded that these cells were the direct descendants of those cells labelled in the graft. There was no evidence of re-utilization of the isotope label. Most of the cells originally labelled in the graft either lost their label by multiple divisions or were replaced by unlabelled cells; although the epithelial-reticular cells remained heavily labelled. The importance of this last finding is discussed. [ABSTRACT FROM AUTHOR]