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Experiment/Payload Overview

Brief Summary

The Mouse Antigen-Specific CD4+ T Cell Priming and Memory Response during Spaceflight (Mouse Immunology) investigation studies specific mechanisms of immune system activation, and whether immune system cells exposed to challenges before flight retain the "memory" to fight challenges during space flight. Space Explorers on future long-duration space missions may require preflight vaccinations or other precautions to prevent infection during space travel if immune memory is not retained.

Principal Investigator

Millie Hughes-Fulford, Ph.D., University of California, San Francisco, San Francisco, CA, United States

Co-Investigator(s)/Collaborator(s)

Tammy T. Chang, Ph.D., M.D., University of California, San Francisco, San Francisco, CA, United States

Payload Developer

Ames Research Center, Moffett Field, CA, United States

Sponsoring Space Agency

National Aeronautics and Space Administration (NASA)

Sponsoring Organization:

Exploration Systems Mission Directorate (ESMD)

ISS Expedition Duration:

March 2010 - September 2010

Expeditions Assigned

23/24

Previous ISS Missions

STS-131/19A is the first mission for Mouse Immunology.

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Experiment/Payload Description

Research Summary

• The Mouse Antigen-Specific CD4+ T Cell Priming and Memory Response during Spaceflight (Mouse Immunology) determines whether antigen-specific CD4+ T cell priming in vivo is inhibited or dysfunctional during space flight.



• This investigations will also determine whether antigen-specific CD4+ memory T cells are maintained normally during space flight and able to mount robust secondary responses.



• This investigation is important because space explorers on future long-duration missions beyond low Earth orbit may require vaccinations to prevent infection during space travel.

Description

The Mouse Antigen-Specific CD4+ T Cell Priming and Memory Response during Spaceflight (Mouse Immunology) investigation determines whether immune responses can be initiated during space flight, and answers the question of whether memory CD4+ T cells (the mediators of immune protection after vaccinations are maintained and able to mount secondary responses. This is important issue because the immunity boost provided by vaccination is dependent upon the maintenance and function of memory T cells. Memory are functional differentiated, long-lived, and more resistant to apoptosis, controlled cell death. For this reason, they must be investigated in a separate set of experiments from normal T cells. Secondary immune responses mediated by memory cells are more rapid and efficient at clearing antigens and pathogens. Since immune protection by vaccines are mediated by memory T cells, deciphering whether memory responses are effective during space flight will determine whether preflight vaccinations may be useful countermeasures to future long-duration space explorers. Once the samples are returned to Earth the PI utilizes standard laboratory techniques to determine the effects of microgravity on the immune system cells of the rodents.

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Applications

Space Applications

Space flight immunosuppression is a significant obstacle to long-term human space travel. Of foremost concern is whether space travelers may be able to generate effective protective immune responses against infections while in space. Using an innovative mouse experimental model, this set of experiments will test whether initial specific activation of T cells is intact and whether memory T cell function is maintained during space flight.

Earth Applications

Understanding the mechanisms of immune regulation is critical to the design of rational therapeutic interventions of these various disease processes. The immunosuppression observed during space flight provides important insight into the role of gravity in the generation of normal immune responses. Deciphering the mechanisms of space flight immunosuppression will provide a more complete picture of the important factors necessary for successful immune responses that may be masked in Earth-based experiments in the presence of gravity. These gravity-sensitive factors may hold the key to our ability to manipulate the immune system and develop therapeutic interventions that will treat the various disease processes affected by immunodysregulation. Dysregulated immune tolerance (overactive immune system) is linked to autoimmune diseases such as type I diabetes mellitus, systemic lupus erythematosus, psoriasis, rheumatoid arthritis, and multiple sclerosis. On the other hand, many disease processes result from immunosuppression (underactive immune system).

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Operations

Operational Requirements

On orbit the mice AEM are relatively self-sufficient. The AEM contains enough food and water to house the mice safely and effectively for the mission duration. An astronaut will check the health status of the mice on a daily basis, by assessing them through the viewing window on the AEM.

Operational Protocols

Sixteen (16) mice are flown in the shuttle middeck housed in two animal enclosure modules (AEMs), 8 mice per each AEM. Half of the mice in both the group that flew to space and the group that stayed on Earth received transgenic thymus cells (T cells), a white blood cell and the immune system's first line of defense, which were exposed to a foreign protein, ovalbumin (OVA), challenge preflight and can retain the memory of how to rapidly respond to future OVA challenges. The other half of the mice were "naive," and their T cells were not exposed to a challenge until immediately after they returned from space. Flight and ground control mice are housed under the same environmental conditions (temperature, light/dark cycle, humidity, oxygen levels and carbon dioxide levels). All mice will receive the same full access to food and water. Upon return to Earth, the AEMs will be returned to the research team for analysis.

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Results/More Information

Information Pending

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Related Web Sites

Flight Systems Implementation

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Publications

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Ground Based Results Publications

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ISS Patent Publications

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Related Publications

• Hughes-Fulford M ,Rodenaker K ,Jütting U ,Reduction of anabolic signals and alteration of osteoblast nuclear morphology in microgravity Cellular Biochemistsry 2006 99 435-449
• Boonyaratanakornkit J B,Cogoli A ,Li C F,Schopper T ,Pippia P ,Galleri G ,Meloni M A,Hughes-Fulford M ,Key gravity-sensitive signaling pathways drive T cell activation The Journal of the Federation of American Societies for Experimental Biology 2005 19 2020-2022
• Hughes-Fulford M ,Function of the cytoskeleton in gravisensing during spaceflight Advances in Space Research 2003 32 1585-1593
• Hatton J P,Gaubert F ,Cazenave J P,Schmitt D ,Microgravity modifies protein kinase C isoform translocation in the human monocytic cell line U937 and human peripheral blood T-cells Journal of Cellular Biochemistry 2002 87 39-50
• Hughes-Fulford M ,The role of signaling pathways in osteoblast gravity perception Journal of Gravitational Physiology Journal of Gravitational Physiology 2002 9 257-260

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Images

Image of the Animal Enclosure Module which will house the rodents used in the Mouse Immunology investigation. Image courtesy of Ames Research Center, Moffett Field, CA.

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