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Project Title:  The Impact of an ISS Mission on the Anti-Viral and Functional Properties of NK-cells, T-cells, B-cells and Dendritic Cells Reduce
Fiscal Year: FY 2023 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 06/01/2016  
End Date: 05/31/2024  
Task Last Updated: 09/28/2023 
Download report in PDF pdf
Principal Investigator/Affiliation:   Simpson, Richard  Ph.D. / University of Arizona 
Address:  College of Agriculture and Life Sciences; College of Medicine 
1177 E. Fourth Street, Room 308, Shantz Building 
Tucson , AZ 85721-0001 
Email: rjsimpson@email.arizona.edu 
Phone: 713-397-0121  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: University of Arizona 
Joint Agency:  
Comments: NOTE: Formerly at University of Houston until September 2017 move to University of Arizona.  
Co-Investigator(s)
Affiliation: 
Bigley, Austin  Ph.D. University of Houston 
Laughlin, Mitzi  Ph.D. University of Houston 
LaVoy, Emily  Ph.D. University of Houston 
Rezvani, Katayoun  M.D., Ph.D. University of Texas M D Anderson Cancer Center 
Key Personnel Changes / Previous PI: Per the PI, Dr. Guillaume Spielmann is no longer involved in the study (Ed., 9/28/23)
Project Information: Grant/Contract No. NNX16AG02G 
Responsible Center: NASA JSC 
Grant Monitor: Stenger, Michael  
Center Contact: 281-483-1311 
michael.b.stenger@nasa.gov 
Unique ID: 10854 
Solicitation / Funding Source: 2014-15 HERO NNJ14ZSA001N-MIXEDTOPICS. Appendix E: Behavioral Health & Human Health Countermeasures Topics 
Grant/Contract No.: NNX16AG02G 
Project Type: FLIGHT 
Flight Program: ISS 
TechPort: No 
No. of Post Docs:  
No. of PhD Candidates:  
No. of Master's Candidates:  
No. of Bachelor's Candidates:  
No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Immune:Risk of Adverse Health Event Due to Altered Immune Response
Human Research Program Gaps: (1) IM-101:Evaluate the effects of deep-space radiation on immune dysfunction, as an additional hazard to the effects of psychophysiological stress and weightlessness.
(2) IM-105:Identify immune biomarkers that correlate with known spaceflight-related immune dysfunction and immune outcomes, as a first step in designing in-flight monitoring paradigms.
Flight Assignment/Project Notes: NOTE: End date changed to 5/31/2024 (original end date was 5/31/2019) per T. Sirmons/JSC (Ed., 5/16/23)

NOTE: End date changed to 12/31/2022 (original end date was 5/31/2019) per NSSC information (Ed., 1/17/22)

NOTE: End date changed to 12/31/2021 (original end date was 5/31/2019) per NSSC information (Ed., 2/22/21)

NOTE: End date changed to 12/31/2020 (original end date was 5/31/2019) per NSSC information (Ed., 7/2/19)

Task Description: NOTE: This is an integrated project consisting of Dr. Brian Crucian's "Functional Immune Alterations, Latent Herpesvirus Reactivation, Physiological Stress, and Clinical Incidence Onboard the International Space Station" directed research; and Dr. Richard Simpson's "The Impact of an ISS Mission on the Anti-Viral and Functional Properties of NK-cells, T-cells, B-cells and Dendritic Cells," Dr. Kanokporn Rithidech's "Effects of Space Flights on the Proteome of Astronauts' Plasma," and Dr. Honglu Wu's "DNA Damage in the ISS Astronaut's Lymphocytes and Their Association with Stress-Induced Immune Dysfunction" solicited research.

Immune system dysregulation is known to occur after both short and long-duration spaceflight, which may leave astronauts at risk of an adverse health event during exploration-class missions. The consistent and profound observation that spaceflight induces latent viral reactivation is a strong indication that immunity is compromised in flight. Moreover, the viruses themselves pose a very real risk to the crew and may compromise their safety and jeopardize mission success. It is pertinent therefore to comprehensively determine how spaceflight impacts the anti-viral properties of the immune system so that effective countermeasures can be developed to mitigate these risks. The parent ‘Functional Immune’ study will markedly advance our understanding in this area and the present proposal aims to contribute by determining the impact of an International Space Station (ISS) mission of the anti-viral properties of NK-cells and T-cells, and the function of B-cells and dendritic cells (DCs). In our ongoing ISS flight study (‘Salivary Markers’), we have found that NK-cell function is drastically impaired during flight and that latent viral reactivation still occurs despite a robust expansion of viral-specific T-cells. It is possible, therefore, that it is the anti-viral capabilities of T-cells and NK-cells that are compromised in flight and we propose to address this question here using both standard and cutting-edge analytical techniques (CyTOF). We will also address the paucity of spaceflight data on B-cells and dendritic cells by assessing B-cell responses to viral peptide stimulation and the differentiation of monocytes to dendritic cells, their antigen uptake capabilities, and ability to activate and expand autologous viral-specific T-cells. All assays will be performed in crewmembers and healthy controls before, during, and after spaceflight using blood volumes that are conducive to the restrictions associated with flight experiments. The studies described in this proposal will make a significant contribution to the parent ‘Functional Immune’ study and will allow us to determine if spaceflight affects the anti-viral properties of cellular and humoral-mediated immunity. On conclusion of this study, it is expected that all ‘immune risks’ will be identified and the focus can shift to the development of countermeasures to preserve crew ‘immune health’ during future exploration-class spaceflight mission.

Research Impact/Earth Benefits:

Task Progress & Bibliography Information FY2023 
Task Progress: The study was initiated in August 2016. As of July 2023, we have completed sample collection for 11 astronauts and 11 controls. A total of 5 participants (3 astronauts and 2 controls) were dropped from the study after the L-45/L-180 sample collection for logistical reasons. Dr. LaVoy at the University of Houston has completed sample analysis of the monocyte-dendritic cell differentiation function. Data are currently being analyzed. Dr. Rezvani’s group at MD Anderson Cancer Center were responsible for detailed immunophenotyping and NK-cell functional assays. They have completed all of the immunophenotyping work and have sent the raw data to the PI (Dr. Simpson) for analysis. While the immunophenotyping work was successful, they did, however, report problems with cell viability for many samples, most likely due to the samples being ‘aged’ for 48h prior to cryopreservation. This has, unfortunately, limited the number of samples we have been able to get usable NK-cell functional data from. Cryopreserved samples were shipped to the PI’s laboratory at the University of Arizona for the analysis of effector lymphocyte function against a range of tumor target cells. While we had similar problems with cell viability, we were able to expand effector lymphocyte populations in vitro (using zoledronic acid and IL-2) and test their function against multiple tumor target cells in a subset of samples. These data are currently being analyzed.

Bibliography: Description: (Last Updated: 09/27/2023) 

Show Cumulative Bibliography
 
Articles in Peer-reviewed Journals Mylabathula PL, Li L, Bigley AB, Markofski MM, Crucian BE, Mehta SK, Pierson DL, Laughlin MS, Rezvani K, Simpson RJ. "Simulated microgravity disarms human NK-cells and inhibits anti-tumor cytotoxicity in vitro. " Acta Astronaut. 2020 Sep;174:32-40. http://www.sciencedirect.com/science/article/pii/S009457652030151X , Sep-2020
Articles in Peer-reviewed Journals Kunz HE, Agha NH, Hussain M, LaVoy EC, Smith KA, Mylabathula P, Diak D, Baker FL, O'Connor DP, Bond RA, Katsanis E, Bollard CM, Simpson RJ. "The effects of ß1 and ß1+2 adrenergic receptor blockade on the exercise-induced mobilization and ex vivo expansion of virus-specific T cells: Implications for cellular therapy and the anti-viral immune effects of exercise. " Cell Stress Chaperones. 2020 Aug 10;25:993-1012. https://doi.org/10.1007/s12192-020-01136-7 ; PMID: 32779001; PMCID: PMC7591642 , Aug-2020
Articles in Peer-reviewed Journals Baker FL, Bigley AB, Agha NH, Pedlar CR, O'Connor DP, Bond RA, Bollard CM, Katsanis E, Simpson RJ. "Systemic ß-adrenergic receptor activation augments the ex vivo expansion and anti-tumor activity of V?9Vd2 T-cells." Front Immunol. 2020 Jan 24;10:3082. https://doi.org/10.3389/fimmu.2019.03082 ; PMID: 32038628; PMCID: PMC6993603 , Jan-2020
Articles in Peer-reviewed Journals Agha NH, Mehta SK, Rooney BV, Laughlin MS, Markofski MM, Pierson DL, Katsanis E, Crucian BE, Simpson RJ. "Exercise as a countermeasure for latent viral reactivation during long duration space flight." FASEB J. First published: 03 January 2020. https://doi.org/10.1096/fj.201902327R ; PubMed PMID: 31908052 , Jan-2020
Articles in Peer-reviewed Journals Agha NH, Baker FL, Kunz HE, Spielmann G, Mylabathula PL, Rooney BV, Mehta SK, Pierson DL, Laughlin MS, Markofski MM, Crucian BE, Simpson RJ. "Salivary antimicrobial proteins and stress biomarkers are elevated during a 6-month mission to the International Space Station." J Appl Physiol (1985). 2019 Nov 21. [Epub ahead of print]. https://doi.org/10.1152/japplphysiol.00560.2019 ; PubMed PMID: 31751178 , Nov-2019
Articles in Peer-reviewed Journals Bigley AB, Agha NH, Baker FL, Spielmann G, Kunz HE, Mylabathula PL, Rooney B, Laughlin MS, Pierson DL, Mehta SK, Crucian BE, Simpson RJ. "NK-cell function is impaired during long-duration spaceflight." J Appl Physiol (1985). 2019 Apr 1;126(4):842-53. Epub 2018 Nov 1. https://doi.org/10.1152/japplphysiol.00761.2018 ; PubMed PMID: 30382809 , Apr-2019
Articles in Peer-reviewed Journals Graff RM, Kunz HE, Agha NH, Baker FL, Laughlin M, Bigley AB, Markofski MM, LaVoy EC, Katsanis E, Bond RA, Bollard CM, Simpson RJ. "ß2-adrenergic receptor signaling mediates the preferential mobilization of differentiated subsets of CD8+ T-cells, NK-cells and non-classical monocytes in response to acute exercise in humans." Brain Behav Immun. 2018 Aug 30. [Epub ahead of print]. https://doi.org/10.1016/j.bbi.2018.08.017 ; PMID: 30172948 , Aug-2018
Articles in Peer-reviewed Journals Kunz HE, Spielmann G, Agha NH, O'Connor DP, Bollard CM, Simpson RJ. "A single exercise bout augments adenovirus-specific T-cell mobilization and function." Physiol Behav. 2018 Oct 1;194:56-65. Epub 2018 Apr 30. https://doi.org/10.1016/j.physbeh.2018.04.035 ; PubMed PMID: 29723594 , Oct-2018
Project Title:  The Impact of an ISS Mission on the Anti-Viral and Functional Properties of NK-cells, T-cells, B-cells and Dendritic Cells Reduce
Fiscal Year: FY 2016 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 06/01/2016  
End Date: 12/31/2022  
Task Last Updated: 06/22/2016 
Download report in PDF pdf
Principal Investigator/Affiliation:   Simpson, Richard  Ph.D. / University of Arizona 
Address:  College of Agriculture and Life Sciences; College of Medicine 
1177 E. Fourth Street, Room 308, Shantz Building 
Tucson , AZ 85721-0001 
Email: rjsimpson@email.arizona.edu 
Phone: 713-397-0121  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: University of Arizona 
Joint Agency:  
Comments: NOTE: Formerly at University of Houston until September 2017 move to University of Arizona.  
Co-Investigator(s)
Affiliation: 
Bigley, Austin  Ph.D. University of Houston 
Laughlin, Mitzi  Ph.D. University of Houston 
LaVoy, Emily  Ph.D. University of Houston 
Spielmann, Guillaume  Ph.D. Louisiana State University 
Rezvani, Katayoun  M.D., Ph.D. University of Texas M D Anderson Cancer Center 
Project Information: Grant/Contract No. NNX16AG02G 
Responsible Center: NASA JSC 
Grant Monitor: Norsk, Peter  
Center Contact:  
Peter.norsk@nasa.gov 
Unique ID: 10854 
Solicitation / Funding Source: 2014-15 HERO NNJ14ZSA001N-MIXEDTOPICS. Appendix E: Behavioral Health & Human Health Countermeasures Topics 
Grant/Contract No.: NNX16AG02G 
Project Type: FLIGHT 
Flight Program: ISS 
TechPort: No 
No. of Post Docs:  
No. of PhD Candidates:  
No. of Master's Candidates:  
No. of Bachelor's Candidates:  
No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Immune:Risk of Adverse Health Event Due to Altered Immune Response
Human Research Program Gaps: (1) IM-101:Evaluate the effects of deep-space radiation on immune dysfunction, as an additional hazard to the effects of psychophysiological stress and weightlessness.
(2) IM-105:Identify immune biomarkers that correlate with known spaceflight-related immune dysfunction and immune outcomes, as a first step in designing in-flight monitoring paradigms.
Flight Assignment/Project Notes: NOTE: End date changed to 12/31/2022 (original end date was 5/31/2019) per NSSC information (Ed., 1/17/22)

Task Description: NOTE: This is an integrated project consisting of Dr. Brian Crucian's "Functional Immune Alterations, Latent Herpesvirus Reactivation, Physiological Stress, and Clinical Incidence Onboard the International Space Station" directed research; and Dr. Richard Simpson's "The Impact of an ISS Mission on the Anti-Viral and Functional Properties of NK-cells, T-cells, B-cells and Dendritic Cells," Dr. Kanokporn Rithidech's "Effects of Space Flights on the Proteome of Astronauts' Plasma," and Dr. Honglu Wu's "DNA Damage in the ISS Astronaut's Lymphocytes and Their Association with Stress-Induced Immune Dysfunction" solicited research.

Immune system dysregulation is known to occur after both short and long-duration spaceflight, which may leave astronauts at risk of an adverse health event during exploration-class missions. The consistent and profound observation that spaceflight induces latent viral reactivation is a strong indication that immunity is compromised in flight. Moreover, the viruses themselves pose a very real risk to the crew and may compromise their safety and jeopardize mission success. It is pertinent therefore to comprehensively determine how spaceflight impacts the anti-viral properties of the immune system so that effective countermeasures can be developed to mitigate these risks. The parent ‘Functional Immune’ study will markedly advance our understanding in this area and the present proposal aims to contribute by determining the impact of an International Space Station (ISS) mission of the anti-viral properties of NK-cells and T-cells, and the function of B-cells and dendritic cells (DCs). In our ongoing ISS flight study (‘Salivary Markers’), we have found that NK-cell function is drastically impaired during flight and that latent viral reactivation still occurs despite a robust expansion of viral-specific T-cells. It is possible, therefore, that it is the anti-viral capabilities of T-cells and NK-cells that are compromised in flight and we propose to address this question here using both standard and cutting-edge analytical techniques (CyTOF). We will also address the paucity of spaceflight data on B-cells and dendritic cells by assessing B-cell responses to viral peptide stimulation and the differentiation of monocytes to dendritic cells, their antigen uptake capabilities, and ability to activate and expand autologous viral-specific T-cells. All assays will be performed in crewmembers and healthy controls before, during, and after spaceflight using blood volumes that are conducive to the restrictions associated with flight experiments. The studies described in this proposal will make a significant contribution to the parent ‘Functional Immune’ study and will allow us to determine if spaceflight affects the anti-viral properties of cellular and humoral-mediated immunity. On conclusion of this study, it is expected that all ‘immune risks’ will be identified and the focus can shift to the development of countermeasures to preserve crew ‘immune health’ during future exploration-class spaceflight mission.

Research Impact/Earth Benefits:

Task Progress & Bibliography Information FY2016 
Task Progress: New project for FY2016.

Bibliography: Description: (Last Updated: 09/27/2023) 

Show Cumulative Bibliography
 
 None in FY 2016