Childhood Adiposity Associated With Expanded Effector Memory CD8+ and Vδ2+Vγ9+ T Cells

J Clin Endocrinol Metab. 2021 Sep 27;106(10):e3923-e3935. doi: 10.1210/clinem/dgab433.

Abstract

Context: Adult obesity is associated with chronic low-grade inflammation and may give rise to future chronic disease. However, it is unclear whether adiposity-related inflammation is already apparent in childhood.

Objective: To study associations between child adiposity measures with circulating monocytes and naive and memory subsets in CD4, CD8, and γδ T cell lineages.

Methods: Ten-year-old children (n = 890) from the Generation R Cohort underwent dual-energy x-ray absorptiometry and magnetic resonance imaging for body composition (body mass index [BMI], fat mass index [FMI], android-to-gynoid fat mass ratio, visceral fat index, liver fat fraction). Blood samples were taken for detailed immunophenotyping of leukocytes by 11-color flow cytometry.

Results: Several statistically significant associations were observed. A 1-SD increase in total FMI was associated with +8.4% (95% CI 2.0, 15.2) Vδ2+Vγ9+ and +7.4% (95% CI 2.4, 12.5) CD8+TEMRO cell numbers. A 1-SD increase in visceral fat index was associated with +10.7% (95% CI 3.3, 18.7) Vδ2+Vγ9+ and +8.3% (95% CI 2.6, 14.4) CD8+TEMRO cell numbers. Higher android-to-gynoid fat mass ratio was only associated with higher Vδ2+Vγ9+ T cells. Liver fat was associated with higher CD8+TEMRO cells but not with Vδ2+Vγ9+ T cells. Only liver fat was associated with lower Th17 cell numbers: a 1-SD increase was associated with -8.9% (95% CI -13.7, -3.7) Th17 cells. No associations for total CD8+, CD4+ T cells, or monocytes were observed. BMI was not associated with immune cells.

Conclusion: Higher Vδ2+Vγ9+ and CD8+TEMRO cell numbers in children with higher visceral fat index could reflect presence of adiposity-related inflammation in children with adiposity of a general population.

Keywords: child; effector memory T cell; fat mass; gamma delta T cell; inflammation; monocyte.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiposity / physiology*
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / pathology*
  • Child
  • Cohort Studies
  • Cross-Sectional Studies
  • Female
  • Genes, T-Cell Receptor delta
  • Genes, T-Cell Receptor gamma
  • Humans
  • Immunologic Memory / immunology
  • Immunophenotyping
  • Lymphocyte Count
  • Lymphocyte Subsets / metabolism
  • Lymphocyte Subsets / pathology
  • Male
  • Monocytes / pathology
  • Netherlands / epidemiology
  • Pediatric Obesity / blood
  • Pediatric Obesity / epidemiology
  • Pediatric Obesity / immunology*