2. Academic Validation
  3. Exogenous estrogen enhances T cell activation in male primates

Exogenous estrogen enhances T cell activation in male primates

  • Cell Rep. 2025 Aug 22;44(9):116170. doi: 10.1016/j.celrep.2025.116170.
Patricia A Hahn 1,  Joan Escrivà-Font 2,  Eric S Alexander 3,  Kimberly Weisgrau 3,  Tianling Ou 4,  Wenhui He 4,  Daniel O'Hagan 5,  Laura C F Da Silva 5,  Noah J Gurley 5,  Li Lin 6,  Michael D Cameron 6,  Eva Rakasz 3,  Michael Farzan 4,  Joe R Kurian 3,  Saverio Capuano 3rd 3,  Camila R Consiglio 2,  Mauricio A Martins 7
Affiliations

Affiliations

  • 1 Department of Immunology and Microbiology, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation and Technology, Jupiter, FL, USA; The Skaggs Graduate School, The Scripps Research Institute, Jupiter, FL, USA.
  • 2 Systems Immunology Lab, Division of Molecular Hematology, Department of Laboratory Medicine, Lund Stem Cell Center, Lund University, Lund, Sweden.
  • 3 Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI, USA.
  • 4 Division of Infectious Disease, Boston Children's Hospital, Boston, MA, USA; The Center for Integrated Solutions to Infectious Diseases, The Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
  • 5 Department of Immunology and Microbiology, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation and Technology, Jupiter, FL, USA.
  • 6 Drug Metabolism and Pharmacokinetics Core, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation and Technology, Jupiter, FL, USA.
  • 7 Department of Immunology and Microbiology, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation and Technology, Jupiter, FL, USA. Electronic address: mauricio.martins@ufl.edu.
PMID: 40849906 DOI: 10.1016/j.celrep.2025.116170
Abstract

Estrogen influences T cell development and enhances Infection resistance in females, but its immunological effects during gender-affirming hormone therapy (GAHT) remain poorly understood. Here, we characterize immune adaptations in male rhesus macaques (RMs) treated with 17β-estradiol (E2) or placebo over 7 months. E2 therapy suppressed endogenous testosterone production, induced female physical traits, and altered blood cell counts and chemistry profiles. Additionally, E2 treatment attenuated innate immune responses while increasing T cell activation. Following mRNA vaccination, E2-treated RMs exhibited significantly higher frequencies of CCR5+ CD4+ T cells, the primary targets for HIV-1 replication, compared to placebo-treated RMs. Overall, our findings reveal the immunological consequences of estrogen in male primates, emphasizing the need to investigate how supraphysiological E2 levels may affect HIV susceptibility and pathogenesis. This work highlights the potential of RMs as a model for studying immune interventions in the context of GAHT.

Keywords

CP: Immunology; CP: Metabolism; estradiol; gender-affirming hormone therapy; human immunodeficiency virus; mRNA vaccine; nonhuman primates; transgender women.

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