EFFECT OF NEONATAL TREATMENT WITH A GONADOTROPIN-RELEASING-HORMONE ANTAGONIST ON DEVELOPMENTAL-CHANGES IN CIRCULATING LYMPHOCYTE SUBSETS - A LONGITUDINAL-STUDY IN MALE RHESUS-MONKEYS

We have examined changes in circulating lymphocyte subsets from the ne onatal period until adulthood (4 months until 5.5 years of age) in mal e rhesus monkeys, and the impact of neonatal treatment with a GnRH ant agonist (Ant) or Ant and androgen (Ant/And) on these parameters. Absol ute numbers of lymphocytes, B cells, total T lymphocytes, and CD4(+) T cells decreased, neutrophils increased, and CD8+ T cells did not chan ge with age. WBC counts increased between 4 mo and 2 years of age and then fell to neonatal levels over the next tao years. The decline of C D4+ 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 th e exception of WBC counts, these values had normalized by 2 years of a ge. Reduced WBC levels in treated animals persisted through adulthood. CD4+ T cell levels tended to be lower in Ant-treated and higher in An t/And-treated animals than in controls at 4 months of age. CD4+ T cell s 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 a n elevated CD4+/CD8+ T cell ratio that persisted until the onset of ye ar 5. During years 5 and 6, seasonal fluctuations in WBC's and neutrop hils were observed with counts being higher in the breeding (fall) tha n in the nonbreeding (summer) season. The data document that developme ntal changes in circulating immune cells in the rhesus monkey are qual itatively similar to those reported in humans, and provide further evi dence that neonatal treatment of male rhesus monkeys with Ant or Ant/A nd may alter early programming of the immune system. (C) 1998 Elsevier Science Ltd. All rights reserved.