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CD25, the alpha chain of the IL-2 receptor, is expressed on activated effector T cells that mediate immune graft damage. Induction immunosuppression is commonly used in solid organ transplantation and can include antibodies blocking CD25. However, regulatory T cells (Tregs) also rely on CD25 for their proliferation, survival, and regulatory function. Therefore, CD25-blockade may compromise Treg protective role against rejection. We analysed in vitro the effect of basiliximab (BXM) on the viability, phenotype, proliferation and cytokine production of Treg cells. We also evaluated in vivo the effect of BXM on Treg in thymectomized heart transplant children receiving BXM in comparison to patients not receiving induction therapy. Our results show that BXM reduces Treg counts and function in vitro by affecting their proliferation, Foxp3 expression, and IL-10 secretion capacity. In pediatric heart-transplant patients, we observed decreased Treg counts and a diminished Treg/Teff ratio in BXM-treated patients up to 6-month after treatment, recovering baseline values at the end of the 12-month follow up period. These results reveal that the use of BXM could produce detrimental effects on Tregs, and support the evidence suggesting that BXM induction could impair the protective role of Tregs in the period of highest incidence of acute graft rejection.

Atopic dermatitis (AD) has a high incidence in heart-transplant children, and the reason why there is more AD after transplantation is still unknown. We conducted a cross-sectional study comparing 11 AD and 11 non-AD age-matched heart-transplant children, to assess which immune alterations are related to AD in these patients. AD patients had been transplanted at a younger age compared to non-AD, indicating that age at transplant may be determinant in the onset of AD. The earlier thymectomy in AD heart-transplant children favored the presence of more differentiated phenotypes in the T cell compartment. We observed a clear reduction in the T-helper 1/T-helper 2 (Th1/Th2) ratio in AD children. This Th2 polarization was related to eosinophilia and high immunoglobulin E levels, but also to an impaired regulatory T cell (Treg) suppression, which could be secondary to an exhaustion of the Treg compartment. Interestingly, AD patients were free of rejection episodes (0/11) in comparison to non-AD children (4/11). We propose that a predominant Th2 phenotype may prevent the emergence of Th1 responses associated with graft rejection. A more differentiated Treg phenotype could also play a role in preventing acute rejection in the first year posttransplant. Our findings provide useful insights and knowledge for the better understanding of atopic disorders in transplanted children. K E Y W O R D Sallergy, clinical research/practice, comorbidities, heart transplantation/cardiology, immune regulation, immunobiology, pediatrics, T cell biology, thymus/thymic biology, translational research/science

The high discard rate of pediatric donor hearts presents a major challenge for children awaiting heart transplantation. Recent literature identifies several factors that contribute to the disparities in pediatric donor heart usage, including regulatory oversight, the absence of guidelines on pediatric donor heart acceptance, and variation among transplant programs. However, a likely additional contributor to this issue are the behavioral factors influencing transplant team decisions in donor offer scenarios, a topic that has not yet been studied in detail. Behavioral economics and decision psychology provide an excellent foundation for investigating decision‐making in the pediatric transplant setting, offering key insights into the behavior of transplant professionals. We conducted a systematic review of published literature in pediatric heart transplant related to behavioral economics and the psychology of decision‐making. In this review, we draw on paradigms from these two domains in order to examine how existing aspects of the transplant environment, including regulatory oversight, programmatic variation, and allocation systems, may precipitate potential biases surrounding donor offer decisions. Recognizing how human decision behavior influences donor acceptance is a first step toward improving utilization of potentially viable pediatric donor hearts.