T Cell Senescence and Accelerated Immunologic Aging in Children Awaiting Kidney Transplantation
Pediatric Nephrology, Emory University and Children's Healthcare of Atlanta, Atlanta
Dept of Surgery, Emory Transplant Center, Emory University, Atlanta, GA
Meeting: 2013 American Transplant Congress
Abstract number: 238
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 child’s 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). https://atcmeetingabstracts.com/abstract/t-cell-senescence-and-accelerated-immunologic-aging-in-children-awaiting-kidney-transplantation/. Accessed November 22, 2024.« Back to 2013 American Transplant Congress