When it comes to immune cells, "it takes all kinds" isn't too bad a description of what makes for the best composition of our fighting force for warding off viruses, bacteria and incipient tumors. But in a study just published in Science Translational Medicine, Stanford infectious-disease immunologist Catherine Blish, MD, PhD, and her colleagues have found, unexpectedly, that high diversity in the overall population of one particular type of immune cells strongly correlates with an increased likelihood of subsequent infection by HIV.
The investigators had figured that diversity in so-called natural killer cells, or NK cells, would be a strength, not a detriment. “Our hypothesis was wrong,” Blish (much of whose research focuses on NK cells) told me. In this study, it was higher, rather than lower, diversity in this immune-cell population that turned out to be associated with increased HIV susceptibility.
NK cells, fierce white blood cells that help fight viruses and tumors, harbor various combinations of receptors on their surface. Some receptors recognize signs of our other cells’ normalcy, while others recognize signs that a cell is stressed — due, say, to viral infection or cancerous mutation. On recognizing their targeted features on other cells’ surfaces, an NK cell’s “normalcy” receptors tend to inhibit it, while its stress-recognizing receptors activate it.
All told, NK cells can have many thousands of different combinations of these receptors on their surfaces, with each combination yielding a slightly different overall activation threshold. At birth, our NK cells are pretty similar to one another. But as they acquire life experience - largely from viral exposure, Blish thinks - they increasingly diverge in the specific combinations of receptors they carry on their surfaces.
From my news release on the study:
In order to assess the impact of NK-cell diversity on adult humans’ viral susceptibility, Blish and her associates turned to blood samples that had been drawn during the Mama Salama Study, a longitudinal study of just over 1,300 healthy ... Kenyan women. [T]he researchers carried out a precise analysis of NK cells in the women’s blood and observed a strong positive correlation between the diversity of a woman’s NK cell population and her likelihood of becoming infected with HIV.
This correlation held up despite the women's being statistically indistinguishable with respect to age, marital status, knowledge of sexual partners’ HIV status, history of trading sex for money or goods, sexually transmitted disease status or reported frequency of recent unprotected sex.
And the NK-diversity-dependent difference in these women’s likelihood of HIV infection was huge. From my release:
Those with the most NK-cell diversity were 10 times as likely as those with the least diversity to become infected. A 10-fold risk increase based solely on NK-cell diversity is far from negligible, said Blish. “By way of comparison, having syphilis increases the risk of contracting HIV two- to four-fold, while circumcised men’s HIV risk is reduced by a factor of 2.5 or 3,” she said.
These surprising findings could spur the development of blood tests capable of predicting individuals’ susceptibility to viral infection.
Previously: Study: Pregnancy causes surprising changes in how the immune system responds to the flu, Revealed: Epic evolutionary struggle between reproduction and immunity to infectious disease and Our aging immune systems are still in business, but increasingly thrown out of balance
Photo by NIAID