Effect of neonatal treatment with a gonadotropin releasing hormone antagonist on developmental changes in circulating lymphocyte subsets: a longitudinal study in male rhesus monkeys

Abstract

We have examined changes in circulating lymphocyte subsets from the neonatal period until adulthood (4 months until 5.5 years of age) in male rhesus monkeys, and the impact of neonatal treatment with a GnRH antagonist (Ant) or Ant and androgen (Ant\\And) on these parameters. Absolute numbers of lymphocytes, B cells, total T lymphocytes, and CD4 + T cells decreased, neutrophils increased, and CD8+ T cells did not change with age. WBC counts increased between 4 mo and 2 years of age and then fell to neonatal levels over the next two years. The decline of CD4+ T cells in association with stable CD8+ T cell levels resulted in an age-related decrease in the CD4+\\CD8+ T cell ratio. At 4 months of age, WBC’s, lymphocytes, total T cells, CD8+ T cells and B cells were lower in Ant- and Ant\\And-treated animals compared to controls. With the exception of WBC counts, these values had normalized by 2 years of age. Reduced WBC levels in treated animals persisted through adulthood. CD4+ T cell levels tended to be lower in Ant-treated and higher in Ant\\And-treated animals than in controls at 4 months of age. CD4+ T cells remained lower in Ant- than in Ant\\And-treated animals at most ages. The higher CD4+T cell counts in Ant\\And- treated animals resulted in an elevated CD4+\\CD8+T cell ratio that persisted until the onset of year 5. During years 5 and 6, seasonal fluctuations in WBC’s and neutrophils were observed with counts being higher in the breeding (fall) than in the nonbreeding (summer) season. The data document that developmental changes in circulating immune cells in the rhesus monkey are qualitatively similar to those reported in humans, and provide further evidence that neonatal treatment of male rhesus monkeys with Ant or Ant\\And may alter early programming of the immune system.