title: Premature T Cell Senescence in Pediatric CKD.
abstract: An individual's immune function, susceptibility to infection, and response to immunosuppressive therapy are influenced in part by his/her T cell maturation state. Although childhood is the most dynamic period of immune maturation, scant information regarding the variability of T cell maturation in children with renal disease is available. In this study, we compared the T cell phenotype in children with renal failure (n=80) with that in healthy children (n=20) using multiparameter flow cytometry to detect markers of T cell maturation, exhaustion, and senescence known to influence immune function. We correlated data with the degree of renal failure (dialysis or nondialysis), prior immunosuppression use, and markers of inflammation (C-reactive protein and inflammatory cytokines) to assess the influence of these factors on T cell phenotype. Children with renal disease had highly variable and often markedly skewed maturation phenotypes, including CD4/CD8 ratio reversal, increased terminal effector differentiation in CD8+T cells, reduction in the proportion of naïve T cells, evidence of T cell exhaustion and senescence, and variable loss of T cell CD28 expression. These findings were most significant in patients who had experienced major immune insults, particularly prior immunosuppressive drug exposure. In conclusion, children with renal disease have exceptional heterogeneity in the T cell repertoire. Cognizance of this heterogeneity might inform risk stratification with regard to the balance between infectious risk and response to immunosuppressive therapy, such as that required for autoimmune disease and transplantation.
authors.affiliation: Division of Pediatric Nephrology, Department of Pediatrics, Children's Healthcare of Atlanta, Atlanta, Georgia; roshan.punnoose.george@emory.edu.|Division of Pediatric Nephrology, Department of Pediatrics, Emory Transplant Center, Emory University, Atlanta, Georgia; and.
authors.forename: Roshan P
authors.initials: RP
authors.lastname: George
authors.affiliation: Division of Pediatric Nephrology, Department of Pediatrics, Emory Transplant Center, Emory University, Atlanta, Georgia; and.
authors.forename: Aneesh K
authors.initials: AK
authors.lastname: Mehta
authors.affiliation: Division of Pediatric Nephrology, Department of Pediatrics, Emory Transplant Center, Emory University, Atlanta, Georgia; and.
authors.forename: Sebastian D
authors.initials: SD
authors.lastname: Perez
authors.affiliation: Division of Pediatric Nephrology, Department of Pediatrics, Children's Healthcare of Atlanta, Atlanta, Georgia.|Division of Pediatric Nephrology, Department of Pediatrics, Emory Transplant Center, Emory University, Atlanta, Georgia; and.
authors.forename: Pamela
authors.initials: P
authors.lastname: Winterberg
authors.affiliation: Division of Surgery, Duke University, Durham, North Carolina.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Cheeseman
authors.affiliation: Division of Pediatric Nephrology, Department of Pediatrics, Emory Transplant Center, Emory University, Atlanta, Georgia; and.
authors.forename: Brandi
authors.initials: B
authors.lastname: Johnson
authors.affiliation: Division of Surgery, Duke University, Durham, North Carolina.
authors.forename: Jean
authors.initials: J
authors.lastname: Kwun
authors.affiliation: Division of Surgery, Duke University, Durham, North Carolina.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Monday
authors.affiliation: Division of Surgery, Duke University, Durham, North Carolina.
authors.forename: Linda
authors.initials: L
authors.lastname: Stempora
authors.affiliation: Division of Pediatric Nephrology, Department of Pediatrics, Children's Healthcare of Atlanta, Atlanta, Georgia.|Division of Pediatric Nephrology, Department of Pediatrics, Emory Transplant Center, Emory University, Atlanta, Georgia; and.
authors.forename: Barry
authors.initials: B
authors.lastname: Warshaw
authors.affiliation: Division of Pediatric Nephrology, Department of Pediatrics, Children's Healthcare of Atlanta, Atlanta, Georgia.|Division of Pediatric Nephrology, Department of Pediatrics, Emory Transplant Center, Emory University, Atlanta, Georgia; and.|Division of Surgery, Duke University, Durham, North Carolina.
authors.forename: Allan D
authors.initials: AD
authors.lastname: Kirk
mesh_terms: D000293:Adolescent; D016922:Cellular Senescence; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D051436:Renal Insufficiency, Chronic / Q000276:immunology*; D013601:T-Lymphocytes / Q000502:physiology*; D013997:Time Factors; D055815:Young Adult
keywords: Chronic Kidney Disease; Dialysis; T cell maturation; pediatric kidney transplantation