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Exogenous estrogen enhances T cell activation in male primates

Hahn, Patricia A ; Escrivà-Font, Joan LU orcid ; Alexander, Eric S ; Weisgrau, Kimberly ; Ou, Tianling ; He, Wenhui ; O'Hagan, Daniel ; Da Silva, Laura C F ; Gurley, Noah J and Lin, Li , et al. (2025) In Cell Reports 44(9).
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.... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cell Reports
volume
44
issue
9
article number
116170
publisher
Cell Press
external identifiers
  • pmid:40849906
  • scopus:105013635657
ISSN
2211-1247
DOI
10.1016/j.celrep.2025.116170
language
English
LU publication?
yes
additional info
Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.
id
59a48be7-b8ed-4b7d-9e1e-a5383870bfd2
date added to LUP
2025-09-17 11:15:22
date last changed
2025-09-18 12:31:07
@article{59a48be7-b8ed-4b7d-9e1e-a5383870bfd2,
  abstract     = {{<p>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.</p>}},
  author       = {{Hahn, Patricia A and Escrivà-Font, Joan and Alexander, Eric S and Weisgrau, Kimberly and Ou, Tianling and He, Wenhui and O'Hagan, Daniel and Da Silva, Laura C F and Gurley, Noah J and Lin, Li and Cameron, Michael D and Rakasz, Eva and Farzan, Michael and Kurian, Joe R and Capuano, Saverio and Consiglio, Camila R and Martins, Mauricio A}},
  issn         = {{2211-1247}},
  language     = {{eng}},
  month        = {{08}},
  number       = {{9}},
  publisher    = {{Cell Press}},
  series       = {{Cell Reports}},
  title        = {{Exogenous estrogen enhances T cell activation in male primates}},
  url          = {{http://dx.doi.org/10.1016/j.celrep.2025.116170}},
  doi          = {{10.1016/j.celrep.2025.116170}},
  volume       = {{44}},
  year         = {{2025}},
}