Immune system dysregulation and latent viral reactivation has been documented during and after space flight. This is of concern as NASA and other space agencies look ahead to multiple-year missions to the moon and Mars where the risk of an adverse health event due to dysregulated immunity will be considerably higher than during suborbital missions. Although the effects of space travel on both cellular and humoral immunity have been extensively studied, most of these have relied on samples collected before and after the mission. As such, there is a severe lack of data to determine how space travel affects immunity during the actual flight phase of the mission. Moreover, while changes in plasma cytokines and the phenotype and function of T-cells, neutrophils and monocytes have been relatively well studied, current knowledge on how space travel affects natural killer cells (NK)-cell function is limited.
NK-cells are a vital component of the immune system, performing both innate and adaptive functions that are critical to the recognition and destruction of malignant and virus-infected cells. Impaired NK-cell function due to space travel could adversely affect immune surveillance against cancer and viruses at a time when crewmembers are exposed to a stressful, high-radiation environment that promotes latent viral reactivation and possibly tumorigenesis. The primary aim of this study was to determine if NK-cell function is impaired during a six-month mission to the International Space Station (ISS). A secondary aim was to explore potential mechanisms for this anticipated reduction in NK-cell function, including changes in NK-cell phenotype differences between experienced and less-experienced crewmembers, and the involvement of plasma-associated factors.
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Saliva, blood, and 24-hour urine collection samples were completed preflight (L-180 and -60), during flight (FD90), one day prior to return (R-1), and postflight (R+0, R+18, R+33, and R+66). These samples, plus an additional inflight sample (FD180), were collected from a crewmember who spent 340 days on the ISS. The investigators compared changes in NK-cell phenotype and function in eight crewmembers who completed a six-month mission to the ISS with healthy controls who remained on Earth. They also quantified viral DNA against the latent herpesviruses cytomegalovirus (CMV), Epstein-Barr virus (EBV), Varicella zoster virus (VZV) and Herpes simplex virus 1 (HSV-1) using both saliva and urine samples collected from the crewmembers and the ground-based controls and measured Immunoglobulin G (IgG) antibody titers against each of these viruses in plasma.
Latent viral reactivation was more evident in ISS crewmembers than in controls, but latent viral reactivation did not appear to be related to the changes in NK-cell function during space flight. The investigators observed reactivations of CMV, HSV-1 and EBV in some ISS crewmembers but did not see a single incidence of VZV reactivation despite VZV shedding being previously recorded. Investigators suspect that the lack of shedding is due to crewmembers receiving the shingles vaccine.
NK-cell cytotoxic activity (NKCA) against K562 leukemia targets in vitro was reduced by approximately 50% on FD90 in ISS crewmembers but not controls. This decrease was more pronounced in crewmembers on their first space mission compared to crewmembers who have flown previously. The crewmember who remained on the ISS for approximately one year did not show declines in NKCA against K562 until late in the mission (R-1 and R+0). NK-cell numbers, expression of activating and inhibitory receptors, target cell binding, and expression and degranulation of perforin and granzyme b were unaltered with space flight. Similarly, exposing the NK-92 cell line to sera collected at different mission time-points did not affect NKCA.
LaVoy EC, Bollard CM, Hanley PJ, O'Connor DP, Lowder TW, Bosch JA, and Simpson RJ. A single bout of dynamic exercise by healthy adults enhances the generation of monocyte-derived-dendritic cells. Cellular Immunology.
2015. February 25; 295(1):52-59. [
Spielmann G, Agha NH, Kunz H, Simpson RJ, Crucian BE, Mehta SK, Laughlin MS, and Campbell J. B cell homeostasis is maintained during long-duration spaceflight. Journal of Applied Physiology (1985).
2019. February 1; 126(2):469-476. [DOI]
Bigley AB, Agha NH, Baker FL, Spielmann G, Kunz HE, Mylabathula PL, Rooney BV, Laughlin MS, Mehta SK, Pierson DL, Crucian BE, and Simpson RJ. NK cell function is impaired during long-duration spaceflight. Journal of Applied Physiology (1985).
2019. April 1; 126(4):842-853. [DOI]
Spielmann G, Laughlin MS, Kunz H, Crucian BE, Quiriarte HD, Mehta SK, Pierson DL, and Simpson RJ. Latent viral reactivation is associated with changes in plasma antimicrobial protein concentrations during long-duration spaceflight. Acta Astronautica.
2018. May;146:111-6. [DOI]
Archive is complete. Data sets are not publicly available but can be requested.+ Request data
Alpha amylase, saliva
C-reactive protein, saliva
Dehydroepiandrosterone (DHEA), saliva
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Epstein-Barr virus nuclear antigen (EBNA)
Herpes simplex virus (HSV)
Mean corpuscular volume
Natural killer cells (NK-cells)
Red blood cells
Varicella-zoster virus (VZV)
Human Research Program (HRP) Human Research Roadmap (HRR) Information
Crew health and performance is critical to successful human exploration beyond low Earth orbit.
The Human Research Program (HRP) investigates and mitigates the highest risks to human health
and performance, providing essential countermeasures and technologies for human space exploration.
Risks include physiological and performance effects from hazards such as radiation, altered gravity,
and hostile environments, as well as unique challenges in medical support, human factors,
and behavioral health support. The HRP utilizes an Integrated Research Plan (IRP) to identify
the approach and research activities planned to address these risks, which are assigned to specific
Elements within the program. The Human Research Roadmap is the web-based tool for communicating the IRP content.
The Human Research Roadmap is located at: https://humanresearchroadmap.nasa.gov/
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for information of how this experiment is contributing to the HRP's path for risk reduction.
Managing NASA Center
Johnson Space Center (JSC)
Responsible NASA Representative
Johnson Space Center LSDA Office
Project Manager: Eric Gallagher
National Aeronautics and Space Administration (NASA)
Alternate Experiment Name