Abstract
Toll-like receptors (TLRs) are being explored to enhance immunity in HIV cure strategies. The TLR7 agonist GS-9620 promotes immune activation, reactivates latent HIV, and delays viral rebound in some people with HIV. Previous work has shown that biological sex influences TLR7 signaling. This study examined the interplay between biological sex, age, and the sex hormones 17β-estradiol, progesterone, and testosterone on GS-9620’s ability to promote cytokine secretion and activate CD4+ T, CD8+ T, and NK cells ex vivo. Interestingly, sex hormones had no effect on GS-9620–mediated immune activation or cytokine induction. However, we found that GS-9620 activity was influenced by age only in female donors. Further, we found that GS-9620–mediated CD4+ T cell activation was positively correlated with the induction of IFN-γ and IL-12, while CD4+ T cell activation and IL-12 production were negatively correlated with age. Additionally, CD8+ T cell activation was positively correlated with IFN-γ production. Mechanistically, IFN-γ was sufficient to promote higher immune activation of both CD4+ and CD8+ T cells in female versus male donors. In conclusion, biological sex and age, but not sex hormones, influence GS-9620–mediated immune activation. Understanding these factors will help in designing and evaluating future clinical trials using GS-9620 for an HIV cure.
Authors
Carissa S. Holmberg, Callie Levinger, Adam R. Ward, Alberto Bosque
This file is in Adobe Acrobat (PDF) format. If you have not installed and configured the Adobe Acrobat Reader on your system.
Having trouble reading a PDF?
PDFs are designed to be printed out and read, but if you prefer to read them online, you may find it easier if you increase the view size to 125%.
Having trouble saving a PDF?
Many versions of the free Acrobat Reader do not allow Save. You must instead save the PDF from the JCI Online page you downloaded it from. PC users: Right-click on the Download link and choose the option that says something like "Save Link As...". Mac users should hold the mouse button down on the link to get these same options.
Having trouble printing a PDF?
- Try printing one page at a time or to a newer printer.
- Try saving the file to disk before printing rather than opening it "on the fly." This requires that you configure your browser to "Save" rather than "Launch Application" for the file type "application/pdf", and can usually be done in the "Helper Applications" options.
- Make sure you are using the latest version of Adobe's Acrobat Reader.
