Long-Term Alterations of Glucocorticoid Receptor Expression and CD4⁺ T Cells in Adolescent Rhesus Macaques Following Early-Life Adversity

Mar M Sanchez ^1,2, Leonidas Panagiotakopoulos ³, Timothy Hayes ⁴

¹Department of Psychiatry & Behavioral Sciences, School of Medicine, Emory University, Atlanta, GA 30345, USA.
²Department of Developmental and Cognitive Neuroscience, Emory National Primate Research Center, Emory University, Atlanta, GA 30345, USA.
³Department of Pediatrics, Division of Pediatric Endocrinology, School of Medicine, Emory University, Atlanta, GA 30345, USA.
⁴Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA 30345, USA.
⁵Fralin Biomedical Research Institute at Virginia Tech Carilion, Roanoke, VA 24061, USA.
⁶Department of Human Development and Family Science, Virginia Tech, Blacksburg, VA 24061, USA.
⁷Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA.
⁸Department of Biological Sciences, Virginia Tech, Blacksburg, VA 24061, USA.
⁹Department of Psychological and Brain Sciences, University of Massachusetts Amherst, Amherst, MA 01003, USA.
¹⁰Department of Neuroscience & Anatomy, School of Medicine, Virginia Commonwealth University, 1101 East Marshall Street, Richmond, VA 23298, USA.

⁰Department of Psychiatry & Behavioral Sciences, School of Medicine, Emory University, Atlanta, GA 30345, USA.

Biomolecules +

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December 30, 2025

View abstract on PubMed

Summary

Child maltreatment (MALT) causes lasting immune changes in adolescents. Early-life adversity impacts T cells and glucocorticoid receptor gene expression, affecting long-term health.

Area Of Science

Neuroscience
Immunology
Developmental Psychology

Background

Child maltreatment (MALT) is a severe form of early-life adversity (ELA) with significant mental and physical health risks.
Disentangling the effects of postnatal caregiving from heritable factors in MALT research is challenging.

Purpose Of The Study

To investigate the long-term effects of MALT on immune function and inflammation in adolescence.
To control for biological/heritable factors using a cross-fostering design in a macaque model.

Main Methods

Utilized a cross-fostering design in macaques to model MALT and control for genetic influences.
Assessed immunophenotype of peripheral blood mononuclear cells (PBMCs) and glucocorticoid receptor (GR) expression and function in adolescents exposed to MALT.
Analyzed changes in CD4+ T cell subsets (naïve and central memory).

Main Results

MALT was associated with elevated expression of *NR3C1* (glucocorticoid receptor gene) in PBMCs.
Glucocorticoid receptor function, tested via dexamethasone (DEX) response, was not altered by MALT.
MALT exposure reduced naïve CD4+ T cells and increased central memory (Tcm) CD4+ T cells.

Conclusions

Adolescents exposed to MALT exhibit persistent effects on CD4+ T cells and increased *NR3C1* expression.
Despite increased gene expression, glucocorticoid receptor function was not demonstrably enhanced by MALT.
Early-life adversity has enduring implications for cellular glucocorticoid receptor biology and T cell populations.

Keywords:

CD4+ FKBP5 TNFα chronic stress early-life adversity glucocorticoid receptor hair cortisol nonhuman primate