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Published on: March 24, 2015
Longitudinal Kinetics of T Cells and NK Cells After Pediatric Liver Transplant
Ayelet Rosenthal1,2, Sangeeta Kowli3, David M Vu1
1Division of Pediatric Infectious Diseases, Department of Pediatrics, Stanford University, School of Medicine, California, USA.
Insights
Pediatric liver transplant recipients show stable T cell function post-transplant, suggesting earlier prophylaxis cessation or vaccination. Tacrolimus levels may not reflect immune competence.
Area of Science:
- Immunology
- Transplantation Medicine
- Pediatric Care
Background:
- Solid Organ Transplant (SOT) improves survival in end-stage organ failure.
- Immunosuppression's impact on pediatric immune competence post-transplant is poorly understood.
- Current practices lack immune data integration.
Purpose of the Study:
- To assess T cell and NK cell phenotype and function post-pediatric liver transplant.
- To evaluate the impact of immunosuppression on immune competence in pediatric SOT recipients.
- To inform prophylaxis and vaccination strategies using immune data.
Main Methods:
- Collected blood from pediatric liver transplant patients (<18 years) pre- and post-transplant (6, 12 months).
- Utilized cytometry by time-of-flight (CyTOF) to analyze T cell subsets and NK cells.
- Stimulated peripheral blood mononuclear cells (PBMCs) to characterize cytokine and enzyme function.
Main Results:
- Immune cell levels (T cells, Tregs, NK cells) remained stable 6-12 months post-transplant.
- Pro-inflammatory and antiviral T cell functions were not reduced at 6 months and remained stable at 12 months.
- IL-2 production did not correlate with tacrolimus levels, indicating a potential disconnect.
Conclusions:
- T cell function is maintained by 6 months post-liver transplant in pediatric patients.
- Consideration for earlier discontinuation of viral prophylaxis or earlier vaccination initiation is suggested.
- Functional T cell assays may better predict infection susceptibility than tacrolimus levels.
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.
