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Mouse Antigen-Specific CD4+ T Cell Priming and Memory Response during Spaceflight (Mouse Immunology)
04.26.13

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Overview | Description | Applications | Operations | Results | Publications | Imagery

Experiment Overview

This content was provided by Millie Hughes-Fulford, Ph.D., and is maintained in a database by the ISS Program Science Office.

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(s)

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

    • Co-Investigator(s)/Collaborator(s)

  • Joseph S. Tash, Ph.D., University of Kansas Medical Center, Kansas City, KS, United States
  • Stavros Thomopoulos, Ph.D., Washington University, St. Louis, MO, United States
  • Michael D. Delp, Ph.D., University of Florida, Gainesville, FL, United States
  • Eduardo Almeida, Ph.D., Ames Research Center, Moffett Field, CA, United States
  • David Fitzgerald, Ph.D., Oregon Health and Science University, Portland, OR, United States
  • Alan R. Hargens, Ph.D., University of California San Diego, La Jolla, CA, United States
  • Larry F. Hoffman, Ph.D., University of California Los Angeles, Los Angeles, CA, United States
  • Maija Mednieks, Ph.D., University of Connecticut Health Center, Farmington, CT, United States
  • Tammy T. Chang, Ph.D., M.D., University of California, San Francisco, San Francisco, CA, United States

    • Developer(s)

    NASA Ames Research Center, Moffett Field, CA, United States

    Sponsoring Space Agency

    National Aeronautics and Space Administration (NASA)

    Sponsoring Organization

    Human Exploration and Operations Mission Directorate (HEOMD)

    Research Benefits

    Information Pending

    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 Description

    Research Overview

    • 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.

    This research is also expected to contribute data to the current body of research on microgravity effects on the skeletal, cardiovascular, and immune systems, liver and kidney function as well as other physiological systems through a tissue sharing program. Every effort will be made to harvest as many different samples and types of tissue from the mice as possible for other mission specific biomedical research. Positive results from this research may advance our understanding of mechanistic changes that occur in various physiological systems after exposure to microgravity and support overall efforts to reduce health risks to crewmembers. The investigations resulting from the Mouse Immunology tissue sharing program are as follows:

    • Eduardo Almeida, Ph.D., Ames Research Center, Moffett Field, CA
      Determine if the p53 signaling pathway, a key regulatory cell-signaling pathway, is responsible, for space-induced arrest of normal cell proliferation.


    • Michael Delp, Ph.D., University of Florida, Gainesville, FL
      To determine whether microgravity alters arterial vascular structure and key signaling pathways in cerebral arteries, the thoracic and abdominal aorta, mesenteric arteries, femoral arteries, and soleus and gastrocnemius muscle feed arteries.


    • David Fitzgerald, Ph.D., Oregon Health and Science University, Portland, OR
      To determine if the reduced biomechanical forces due to microgravity impair the ability of chondrocytes to maintain healthy articular cartilage, leading to increased cartilage breakdown.


    • Alan R. Hargens, Ph.D., University of California San Diego, La Jolla CA
      To determine if intervertebral disc morphology, cell content, swelling pressure, and glycosaminoglycan (GAG) and proteoglycan (PG) concentrations will significantly decrease following exposure to space flight.


    • Larry Hoffman, Ph.D., University of California Los Angeles, Los Angeles, CA
      Determine if Exposure to microgravity induces synaptic plasticity in the utriculi and sacculi which is manifested in an increase in the density of hair cell synaptic ribbons compared with Earth-gravity controls and determine if the readily releasable pool of vesicles at the active zone of utricular hair cell synapses are hemifused to the presynaptic membrane, and this pool of vesicles is labile to changes in the ambient gravitational environment.


    • Maija Mednieks, Ph.D., University of Connecticut Health Center, Farmington, CT
      Determine if extended weightlessness alters salivary glands and expression of their secretory protein.


    • Joseph S. Tash, Ph.D., University of Kansas Medical Center, Kansas City, KS
      To determine if exposure to microgravity disrupts normal estrous cycling, ovarian structure/function, and uterine horn morphology.


    • Stavros Thomopoulos, Ph.D., Washington University, St. Louis, MO
      To examine the effect of prolonged weightlessness on the biology of tendons and their insertions into bone.

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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

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    Results Publications

      Stabley JN, Dominguez JM, Dominguez CE, Mora Solis FR, Ahlgren J, Behnke BJ, Muller-Delp J, Muller-Delp J, Delp MD.  Spaceflight Reduces Vasoconstrictor Responsiveness of Skeletal Muscle Resistance Arteries in Mice. Journal of Advanced Materials. 2012 11/01/2012; 113(9): 1439-1445. DOI: 10.1152/japplphysiol.00772.2012.
      Zhao L, Tanjung N, Swarnkar G, Ledet E, Yokota H.  Regulation of eIF2? phosphorylation in hindlimb-unloaded and STS-135 space-flown mice. Advances in Space Research. 2012; 50(5): 576-583. DOI: 10.1016/j.asr.2012.05.024.

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    Ground Based Results Publications

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    ISS Patents

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    Related Publications

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    Related Websites
  • Flight Systems Implementation

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    Imagery

    image 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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    Information provided by the investigation team to the ISS Program Scientist's Office.
    If updates are needed to the summary please contact JSC-ISS-Program-Science-Group. For other general questions regarding space station research and technology, please feel free to call our help line at 281-244-6187 or e-mail at JSC-ISS-Research-Helpline.
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