A 'window' into the female immune system

Hormonal changes during a woman's menstrual cycle open a “window of vulnerability:” a time period during which the female reproductive tract is more susceptible to sexually transmitted infections (STIs), Dartmouth researchers have found. Their work may one day lead to better prevention of STIs and better understanding of the pathogenesis of autoimmune diseases and cancer progression. 

The most recent article about these findings was published in the March 2015 issue of Nature Reviews in Immunology. Lead author Charles R. Wira, PhD, of the Geisel School of Medicine at Dartmouth College in Lebanon, New Hampshire, told Contemporary OB/GYN about his team’s work and its importance.

Charles R. Wira, PhD

“We arrived at the hypothesis of a ‘window of vulnerability’ following extensive studies over many years that led to the conclusion that each site in the reproductive tract is separate and distinct in terms of immune protection, that each is hormonally controlled, and that changes in immune function at each site parallel the role of each site in successful reproduction,” he wrote in an email.

“We came to realize that the immune suppression that optimizes conditions for successful implantation and pregnancy might place a women at risk for STIs, especially HIV. This window now has 2 primate studies and one human biopsy study that support our hypothesis.”

To arrive at these findings, Dr. Wira and his colleagues have isolated, purified, and functionally characterized immune cells in the human female reproductive tract using tissues obtained at surgery. They have developed methods that allow studies of hormone, cell-cell and pathogen (bacterial and viral) interactions, focusing on HIV.  

Within the female reproductive tract, the challenge of protection against STIs is coupled with the need to enable successful reproduction, the researchers note in the March article. Specifically, immune protection is dampened during the secretory phase of the cycle to optimize conditions for fertilization and pregnancy, which creates a “window of vulnerability” during which potential pathogens can enter and infect the reproductive tract.

Dr. Wira told Contemporary OB/GYN that his team’s studies could one day benefit clinicians in several ways:

• Without the window, women would be faced with problems of infertility or recurrent miscarriages if suppression is incomplete.

• Closing the window could lower the risk for HIV and other gynecological infections.

• Understanding how the immune system is suppressed locally is now a model for understanding how cancers suppress the immune system to evade destruction. 

• Understanding the regulatory control could increase our understanding of the spectrum of autoimmune diseases, many of which are more common in women than in men.