Longitudinal Kinetics of T Cells and NK Cells After Pediatric Liver Transplant

BACKGROUND: Solid Organ Transplant (SOT) provides a survival advantage for individuals with end organ failure. Little is known about the specific effects of immunosuppression on the competence of the immune system during the post-transplant period especially in the pediatric population, and current immunosuppression and prophylaxis practices are not well informed by immune data. METHODS: Blood samples from pediatric patients < 18 years old were collected prior to and 6- and 12 months after liver transplant. Peripheral blood mononuclear cells (PBMCs) were stimulated with PMA/Ionomycin and the phenotype and function of T cell subsets and NK cells were systematically characterized using cytometry by time-of-flight (CyTOF). RESULTS: In a cohort of 4 pediatric liver transplant patients, levels of CD4+ and CD8+ T cells, Tregs and NK cells at 6- and 12 months following liver transplant were similar to levels before transplant. Upon stimulation, pro-inflammatory, antiviral, and inhibitory T cell cytokines and enzymes were not reduced at 6 months post-transplant and remained stable at 12 months. IL-2 production, a tacrolimus target, from CD4+ and CD8+ T cells did not correlate with tacrolimus levels. CONCLUSION: T cell function was not reduced by 6 months following liver transplant. This suggests that it might be safe to discontinue viral prophylaxis or initiate vaccinations sooner than previously suspected. Tregs functional marker expression was intact by 6 months post-transplant suggesting lower risk of rejection in this cohort. Tacrolimus level may not be a good indication for immunocompetence and T cell functional assays may be more predictive of susceptibility to infection.