Introduction: Childhood is a period of dynamic maturation. Pre-clinical studies indicate that the maturation state of pre-transplant (pre-Tx) immune repertoire influences risks of transplantation, such as susceptibility to infection and response to types of immunosuppression (IS). However, there is scant clinical information regarding T cell maturation in children with chronic renal insufficiency (CRI), particularly the immune variability emerging in childhood and presenting to the clinician planning a childs transplant immune therapy.
Methods: To study influence of CRI and its associated therapies on T cell repertoire, blood obtained from pre-Tx children (n=60) with CRI or on dialysis and normal controls (NC, n=6) was analyzed by multiparameter flow cytometry, specifically interrogating for indices of T cell maturation, exhaustion and senescence. Flow data was correlated to markers of inflammation-CRP and ferritin.
Results: Of the 60 pre-Tx children, 20 on hemodialysis (HD), 20 on peritoneal dialysis (PD), 20 with CRI, not on dialysis; 13 (21.6%) had reversal of CD4/CD8 ratio, not seen in any of the NC. CD4/CD8 reversal was significantly (p= <0.0001) related to exposure to IS for prior disease treatment. While NC displayed a tight, low range of CD8+ terminal effector memory cells (Temra; CCR7-CD45RA+), pre-Tx had a much wider range (13.13 vs. 69.6 respectively). There was significant difference in Temra frequencies in HD vs NC (p =0.05) but none between non-dialysis, HD, or PD. In the pre-Tx group, 22% had elevation (≥25%) in CD8 Temra; 50% in late differentiated effector (CD8, CD28-); 43% in senescent cell (CD8 CD57 high) and 43% in exhausted cell (CD8 PD1 high) populations. Each of these was significantly elevated when compared to respective populations in NC (p <0.001). 63% of patients on dialysis with high CD28- had elevated ferritin and 58% had received prior IS.
Conclusion: CRI and its associated therapies skew T cell repertoire in pre-Tx children towards terminal differentiation, immune senescence and exhaustion, particularly in children receiving prior IS. Cognizance of T cell senescence should enable more customized IS therapy to improve the balance between risk of infections and adequacy of IS.
To cite this abstract in AMA style:George R, Mehta A, Stempora L, Johnson B, Cheeseman J, Sebastian P, Warshaw B, Kirk A. T Cell Senescence and Accelerated Immunologic Aging in Children Awaiting Kidney Transplantation [abstract]. Am J Transplant. 2013; 13 (suppl 5). http://atcmeetingabstracts.com/abstract/t-cell-senescence-and-accelerated-immunologic-aging-in-children-awaiting-kidney-transplantation/. Accessed September 23, 2017.
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