Altered Cytokine Production By Specific Human Peripheral Blood Cell Subsets Immediately Following Spaceflight

摘要

In this study, we have attempted to combine standard immunological assays with the cellular resolving power of the flow cytometer to positively identify the specific cell types involved in spaceflight-induced immune alterations. We have obtained whole blood samples from 27 astronauts collected at three timepoints (L-10, R+0 and R+3) surrounding four recent space shuttle missions. The duration of these missions ranged from 10 to 18 days. Assays performed included serum/urine cortisol, comprehensive subset phenotyping, assessment of cellular activation markers and intracellular cytokine production following mitogenic stimulation. Absolute levels of peripheral granulocytes were significantly elevated following spaceflight, but the levels of circulating lymphocytes and monocytes were unchanged. Lymphocyte subset analysis demonstrated trends towards a decreased percentage of T cells and an increased percentage of B cells. Nearly all of the astronauts exhibited an increased CD4:CD8 ratio, which was dramatic in some individuals. Assessment of memory (CD45RA+) vs. naive (CD45RO+) CD4+ T cell subsets was more ambiguous, with subjects tending to group more as a flight crew. All subjects from one mission demonstrated an increased CD45RA:CD45RO ratio, while all subjects from another Mission demonstrated a decreased ratio. While no significant trend was seen in the monocyte population as defined by scatter, a decreased percentage of the CD14+ CD16+ monocyte subset was seen following spaceflight in all subjects tested. In general, most of the cellular changes described above which were assessed at R+O and compared to L-10 trended to pre-flight levels by R+3. Although no significant differences were seen in the expression of the cellular activation markers CD69 and CD25 following exposure to microgravity, significant alterations were seen in cytokine production in response to mitogenic activation for specific subsets. T cell (CD3+) production of IL-2 was significantly decreased after at R+O as was IL-2 production by both CD4+ and CD8+ T cell subsets for most subjects. Production of IFN(sub gamma) did not appear to be affected by microgravity exposure in either T cells in general or in the CD8+ T cell subset. There was a spaceflight-induced decrease in IFN(sub gamma) production in the CD4+ T cell subset, however it did not reach statistical significance. Serum and urine stress-hormone analysis indicated significant physiologic stresses in astronauts following spaceflight. In summary, these results demonstrate alterations in the peripheral immune system of astronauts immediately after spaceflight of 10 to 18 days duration and support continued research regarding microgravity and immunology (including in-flight sampling) prior to routine long-term spaceflight for astronauts.