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Ovariectomy Increases CD4 + T cell Activation in Simian Immunodeficiency Virus Infection
Author(s) -
McTernan Patrick,
Siggins Robert,
Simon Liz,
Molina Patricia
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.03884
Subject(s) - simian immunodeficiency virus , cd8 , medicine , flow cytometry , immunology , cd38 , t cell , andrology , human immunodeficiency virus (hiv) , biology , immune system , cd34 , stem cell , genetics
People living with HIV (PLWH) have a higher prevalence of alcohol use disorder (AUD), which has been associated with accelerated HIV disease progression. Older PLWH, especially postmenopausal women, are at a greater risk for alcohol‐related problems. Previous studies have shown that chronic binge alcohol (CBA) administration leads to higher simian immunodeficiency virus (SIV) loads and accelerated progression towards end‐stage disease in rhesus macaques. Clinical studies have shown that ovariectomy (OVX) increases T cell activation and serum TNF‐alpha levels. We tested the hypothesis that CBA and ovarian hormone loss, resulting from OVX, increases T cell activation in SIV‐infected female rhesus macaques. CBA or isovolumetric water was administered through an intragastric catheter for 30 minutes, 5 days a week, with peak blood alcohol concentrations reaching 50‐60 mM. After three months of CBA/VEH administration, macaques were infected with SIV Mac251 and 2.5 months later initiated on ART. OVX was performed one month after ART initiation, and study endpoint was ~12 months post‐SIV infection. Blood samples obtained at study end point were used for flow cytometry analysis with FITC‐CD38, PerCP‐CD3, PE‐CD45, Qdot 655‐CD8, ECD‐CD20, APC‐Cy7‐CD4, PE‐Cy7‐CD16, APC‐CD66, Pacific Blue‐CD14, and Am Cyan‐Live Dead, using a BD Biosciences LSRII flow cytometer and FlowJo software (version 10.7.1). Two‐way ANOVA was used to detect significant differences between groups (N = 7‐8/group). At study end‐point, there was a main effect of OVX to increase activated CD4 + CD38 + T cells (p = 0.0171) compared to SHAM. Neither CBA nor OVX had an effect on activation of CD8 + T cells. There was a main effect of OVX (p = 0.0195) and an interaction (p = 0.05) observed for CD4 T cell numbers (cells/ml). Post‐hoc analysis showed higher CD4 T cell number in the CBA/SIV/ART/OVX compared to CBA/SIV/ART/SHAM (p = 0.0174) animals. There were no significant differences between the treatment groups for CD20 + , CD14 + , and CD16 + cells. Our results show that OVX lead to an increase in activation of peripheral CD4 + T cells and an increase in peripheral CD4 + T cells within CBA animals, which could favor a pro‐inflammatory environment and an increase in target cells in SIV‐infected female macaques.