Long Duration Spaceflight Impairs NK-cell Function In Astronauts

Robust immunity is essential for further human exploration of the solar system beyond Earth’s orbit. Immune dysregulation and latent viral reactivation has been documented in astronauts during and after spaceflight, but the effects of long duration missions on the functional properties of NK-cells are not known. PURPOSE: To determine the impact of a 6-month mission to the International Space Station (ISS) on the phenotype and function of NK-cells. METHODS: Blood samples were taken from 6 ISS crewmembers and 6 ground-based controls before launch (L-180 and L-60), in-flight (FD10, FD90, R-1), immediately upon return to Earth (R+0) and up to 66 days following return (R+18, R+33 and R+66). In-flight samples were returned to the terrestrial laboratory within 30-56h of being drawn and immediately processed with the control samples, which were drawn at identical times to the crew. The levels of surface activating (NKG2C) and inhibitory (NKG2A) receptors and intracellular perforin and granzyme-b expression were determined in CD3-/CD56 NK-cells by 4-color flow cytometry, and NK-cell cytotoxicity activity (NKCA) against tumor cells of leukemia (K562), multiple myeloma (U266) and lymphoma (221.AEH and 721.221) origin were determined in a 4h NKCA assay. RESULTS: All crewmembers demonstrated a significant reduction in NKCA during flight (FD90) against all tumor target cells to levels that were (mean ± SE) 42 ± 7% (K562), 49 ± 16% (U266), 28 ± 5% (221.AEH), and 36 ± 10% (721.221) of baseline (L-180) NKCA (p<0.05). FD90 Perforin and granzyme b levels were reduced to 52 ± 7% of baseline levels (p<0.05) and these correlated highly (R2>0.75) with changes in NKCA. In some crewmembers, NKCA remained suppressed at R-1 and up to R+66. NKG2C and NKG2A expression remained unchanged, except in one crewmember who had a massive expansion of NKG2C+ NK-cells and profound shedding of cytomegalovirus in urine at FD90. No significant changes in NKCA or NK-cell phenotype were found in the ground-based controls (p>0.05). CONCLUSION: Long duration spaceflight ‘disarms’ NK-cells of perforin and granzyme b and suppresses their ability to kill a wide range of tumor target cells during the in-flight phase of the mission. Further research is required to develop countermeasures to help maintain normal immune function during exploration class missions