Immune system failures force rodents into space

Space station ISS

Astronaunts have a regular tendency to fall ill on missions, which causes time and money, (not to say discomfort) for all involved. Millie Hughes-Fulford of the Northern California Institute for Research and Education and the University of California at San Francisco, who actually flew on a NASA shuttle in the 1980s, wants to find out why.

Enter the test subjects: 16 JAX Mice from Bar Harbor. The thought is that the mice can help scientists study the effects of space environments on immune systems through their journey on the Space Shuttle Discovery. 

"From the beginning of the U.S. Apollo moon program, we’ve known that about half of our astronauts develop suppressed immune systems, either during flight or shortly afterwards, and we have since learned that non-functioning T cells are at least partly responsible," says Hughes-Fulford, who is also a professor of medicine at the University of California, San Francisco.

T cell failure in space

The key is to discover why T cells stop working in the absence of gravity.

On earth, T cells stop functioning in people with untreated HIV/AIDS, as well as in some elderly people, leading to the development of potentially fatal opportunistic infections.

The immune system normally responds within four hours of exposure to an infectious agent by expressing certain genes. This gene expression, in turn, initiates a series of molecular and cellular reactions that ultimately result in the activation of T cells and other white blood cells, which then migrate to the site of the infection.

The astronauts' immune weaknesses are similar to muscular-skeletal diseases in paralyzed or comatose patients on Earth and to the weakening of the immune system with aging, according to Hughes-Fulford. Hughes-Fulford has cited cases where seemingly healthy astronauts have been diagnosed with shingles, a condition that is common among people over 60.

In one part of the experiment, testing naive T cells, rodents that have not previously been exposed to an infectious agent will live aboard the ISS space station in Animal Enclosure Modules in zero-gravity. The idea is to test one set of rodents in space and another matched set of rodents exposed to gravity on earth. After a set amount of time both sets of rodents will be exposed to OVA, a protein found in egg white that functions as a model of infection. The expectation is that the T cells in the experimental mice will not activate, while the T cells in the control mice will.

"We hope this will allow us to pare down our list of non-expressing genes to a much smaller number of genes, and give us a better handle on what’s happening in humans," said Hughes-Fulford.
The other part of the experiment will test memory T cells, or rodents that have already been exposed to infection. Like the other experiment, the expected outcome is that the memory T cells in the rodents in space will not activate.

Hughes-Fulford explains that memory T cells react much faster and effectively than naive T cells in the presence of the infection agent to which they have been exposed, which is what gives vaccinations their protective effect. "We’re doing this experiment because there is evidence that memory T cells don’t work in microgravity" she says. "Apparently, some astronauts are not protected against diseases they have been inoculated for. And we want to find out why."

"It's not the first time our mice have been in space, but it's pretty neat," Jackson Lab spokeswoman Joyce Peterson says. Two dozen Maine mice joined the space shuttle Endeavor on a mission in 2001 to study the effects of a no-gravity environment on bone density, Peterson adds.

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