Regulatory T‐cells (Tregs) are a subset of T cells generated in the thymus with intrinsic immunosuppressive properties. Phase I clinical trials have shown safety and feasibility of Treg infusion to promote immune tolerance and new studies are ongoing to evaluate their efficacy. During heart transplantation, thymic tissue is routinely discarded providing an attractive source of Tregs. In this study, we developed a GMP‐compatible protocol for expanding sorted thymus‐derived CD3+CD4+CD25+CD127– (Tregs) as well as CD3+CD4+CD25+CD127–CD45RA+ (RA+Tregs) cells. We aimed to understand whether thymic RA+Tregs can be isolated and expanded offering an advantage in terms of stability as it has been previously shown for circulating adult CD45RA+ Tregs. We show that both Tregs and RA+Tregs could be expanded in large numbers and the presence of rapamycin is essential to inhibit the growth of IFN‐γ producing cells. High levels of FOXP3, CTLA4, and CD25 expression, demethylation of the FOXP3 promoter, and high suppressive ability were found with no differences between Tregs and RA+Tregs. After freezing and thawing, all Treg preparations maintained their suppressive ability, stability, as well as CD25 and FOXP3 expression. The number of thymic Tregs that could be isolated with our protocol, their fold expansion, and functional characteristics allow the clinical application of this cell population to promote tolerance in pediatric heart transplant patients.

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Aims:Most reports on the outcome of children who present with heart failure, due to heart muscle disease, are from an era when ventricular assist devices were not available. This study provides outcome data for the current era where prolonged circulatory support can be considered for most children.Methods & Results:Data was retrieved on 100 consecutive children, who presented between 2010 – 2016, with a first diagnosis of unexplained heart failure. Hospital outcome was classified as either death, transplantation, recovery of function or persistent heart failure. Median age at presentation was 24 months and 58% were < 5 years old. Hospital mortality was 12% and 59% received a heart transplant. Most, 79%, of the transplants were carried out on patients with a device. Recovery of function was observed in 18% and 10% stabilised on oral therapy. Eighty-four percent of the deaths occurred in the <5 year old group. Shorter duration of support was associated with survival (34 days in survivors versus 106 in non-survivors, p = 0.01) and 72% were on an assist device at time of death.Conclusion:Heart failure in children who require referral to a transplant unit is a serious illness with a high chance of either transplantation or death. Modifications in assist devices will be required to improve safety, especially for children < 5 years old where the donor wait may be prolonged. The identification of children who may recover function requires further study.

PurposeMost reports on the outcome of children who present with heart failure are from an era when ventricular assist devices (VAD) were not available. This study provides outcome data for the modern era where prolonged circulatory support can be considered for children of all ages.MethodsData on children who presented from 2010–2015, with a first diagnosis of heart failure, excluding those with structural heart disease, was retrieved.ResultsThe median age at presentation, in the 100 children, was 18 months. Overall, hospital mortality was 15%, 50% received a heart transplant, 25% recovered systolic function and 15% stabilised on oral therapy. Mean time from admission to death was 89 days. Most children (63%) were <5 years old and most of the deaths (11/15) occurred in that group. Comparing age groups: mortality was higher (19% versus 8%); transplantation rate was lower (41% versus 65%); VAD use higher (62% versus 48%) and more recovered systolic function (29% versus 19%) in the <5 years versus those ≥5 years. The mean duration of VAD, in those who died in the <5 year group, was 106 days (compared to 61 days in those who survived).ConclusionHeart failure in children which requires referral to a transplant unit remains a very serious illness with a high chance of either transplantation or death. Modifications to the current VAD support will be required to enable this group to survive to either recovery or access to the inadequate heart donor pool.