Premature T Cell Senescence in Pediatric CKD.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • George, RP; Mehta, AK; Perez, SD; Winterberg, P; Cheeseman, J; Johnson, B; Kwun, J; Monday, S; Stempora, L; Warshaw, B; Kirk, AD

Published Date

  • January 2017

Published In

Volume / Issue

  • 28 / 1

Start / End Page

  • 359 - 367

PubMed ID

  • 27413076

Pubmed Central ID

  • 27413076

Electronic International Standard Serial Number (EISSN)

  • 1533-3450

Digital Object Identifier (DOI)

  • 10.1681/ASN.2016010053

Language

  • eng

Conference Location

  • United States