Abstract
Immune system adaptation during spaceflight is a concern in space medicine. Decreased circulating leukocytes observed during and after space flight infer suppressed immune responses and susceptibility to infection. The microgravity aspect of the space environment has been simulated on Earth to study adverse biological effects in astronauts. In this report, the hindlimb unloading (HU) model was employed to investigate the combined effects of solar particle event-like proton radiation and simulated microgravity on immune cell parameters including lymphocyte subtype populations and activity. Lymphocytes are a type of white blood cell critical for adaptive immune responses and T lymphocytes are regulators of cell-mediated immunity, controlling the entire immune response. Mice were suspended prior to and after proton radiation exposure (2 Gy dose) and total leukocyte numbers and splenic lymphocyte functionality were evaluated on days 4 or 21 after combined HU and radiation exposure. Total white blood cell (WBC), lymphocyte, neutrophil, and monocyte counts are reduced by approximately 65%, 70%, 55%, and 70%, respectively, compared to the non-treated control group at 4 days after combined exposure. Splenic lymphocyte subpopulations are altered at both time points investigated. At 21 days post-exposure to combined HU and proton radiation, T cell activation and proliferation were assessed in isolated lymphocytes. Cell surface expression of the Early Activation Marker, CD69, is decreased by 30% in the combined treatment group, compared to the non-treated control group and cell proliferation was suppressed by approximately 50%, compared to the non-treated control group. These findings reveal that the combined stressors (HU and proton radiation exposure) result in decreased leukocyte numbers and function, which could contribute to immune system dysfunction in crew members. This investigation is one of the first to report on combined proton radiation and simulated microgravity effects on hematopoietic, specifically immune cells.
Highlights
It is well established that spaceflight alters immune function [1,2,3,4,5,6] by mechanisms which are poorly understood
At the 4 day time point, the white blood cell (WBC) counts, lymphocyte counts, and neutrophil counts resulted in very similar trends
The WBCs and lymphocytes were decreased in a statistically significant manner in the peripheral blood of animals exposed to 2 Gy with and without hindlimb unloading (HU), compared to the group of animals not suspended and not irradiated (No treatment group, *, Fig. 1A and 1B)
Summary
It is well established that spaceflight alters immune function [1,2,3,4,5,6] by mechanisms which are poorly understood. Factors in the space environment contributing to immune dysregulation during and post-spaceflight include exposure to microgravity, stress, deconditioning (reduced physical activity and shift of fluids), and radiation. Primary immune defense heavily relies on immune cell distribution and function, and is clearly influenced by a combination or synergy of any of the factors described above that exist in the space environment. Of the blood cell types, lymphocytes are the most sensitive to ionizing radiation exposure. T cells, or T lymphocytes, processed in the thymus, secrete lymphokines, which orchestrate signaling to lymphocytes and other immune cells to promote cell activation, proliferation, destroy target cells, and incite macrophages. Blood lymphocytes isolated from astronauts upon re-entry after a prolonged spaceflight exhibit decreased responses in mitogen reactivity, T-lymphocyte proliferation, and IL-2 production [7]
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