Immune changes during space flights in excess of two weeks have been almost exclusively studied by Russian investigators. Most of these studies have compared postflight values with those obtained before flight. In a very few cases, analyses have also been attempted during flight or with samples collected during flight. Studies of cosmonauts during spaceflight have shown that IgG levels were unchanged, whereas IgA and IgM levels were sometimes increased. Additionally, inflight delayed type hypersensitivity testing demonstrated a decrease below the warning level in 1/3 of the cosmonauts tested. Pre- vs. postflight analyses have often revealed a postflight decrease in: PHA-triggered lymphocyte blast transformation; the proliferation index of T-lymphocytes in the xenogeneic graft versus host reaction; the mitogen-induced production of interleukin-2; the presence of certain leukocyte sub sets; and cytotoxic activity of natural killer cells. Other factors that either did not change, or changed in an apparently random manner after flight included: production of alpha and gamma interferon; autoimmune tests; and globulin classes.

Experiments were carried out aboard COSMOS 2044 to determine the effects of spaceflight on immunologically important cell function and distribution. Control groups included vivarium, synchronous, and antiorthostatically suspended rats. In one experiment, rat bone marrow cells were examined in Moscow, for their response to recombinant murine granulocyte/monocyte colony-stimulating factor (GM-CSF). In another experiment, rat spleen and bone marrow cells were stained in Moscow with a variety of antibodies directed against cell surface antigenic markers. These cells were preserved and shipped to the United States for analysis on a flow cytometer. Bone marrow cells from flown and suspended rats showed a decreased response to granulocyte/monocyte colony-stimulating factor compared with bone marrow cells from control rats. Of the spleen cell subpopulations examined from flown rats, only those cells expressing markers for suppressor-cytotoxic T- and helper T-cells showed an increased percentage of stained cells. Bone marrow cells showed an increase in the percentage of cells expressing markers for helper T-cells in the myelogenous population and increased percentages of anti-asialo granulocyte/monocyte-1-bearing interleukin-2 receptor-bearing pan T- and helper T-cells in the lymphocytic population. Cell populations from rats suspended antiorthostatically did not follow the same pattern of distribution of leukocytes as cell populations for flown rats. The results from COSMOS 2044 are similar, but not identical, to earlier results from COSMOS 1887 and confirm that spaceflight can have profound effects on immune system components and activities.

Studies of peripheral blood lymphocytes from astronauts indicate that microgravity depresses T-cell responsiveness. However, this effect has not been examined in cells of peripheral lymphatic tissue, where most lymphocytes are located. In this study, inguinal lymph node lymphocytes from rats flown on the COSMOS 2044 mission were tested for proliferation and interleukin-2 (IL-2) production. Cells cultured with mitogenic lectins, phorbol ester, and calcium ionophore, or T-cell mitogen and lymphokine, were assayed for DNA synthesis by [3H]thymidine incorporation. Lymphocytes incubated with a T-cell mitogen alone also were tested for IL-2 production. Proliferation of lymphocytes from flight rats was not significantly different from controls for any of the mitogens tested. Furthermore, lymph node lymphocytes from flight rats was not significantly different from controls for any of the mitogens tested. Furthermore, lymph node lymphocytes from control and flown rats produced similar amounts of IL-2. Thus microgravity may act on lymphocytes in a tissue-specific manner, a new finding that could impact on the evaluation of spaceflight effects on immunocompetence.

During the Spacelab Life Sciences-2 mission, rats were dissected in space and biosamples were returned to Earth for analysis. Immunologic studies addressed the kinetics of T lymphocyte proliferative responses, cytotoxic activity of natural killer cells, and cytokine production. Experiments were performed by using spleen and bone marrow of rats dissected before flight, during flight, immediately after landing of the space shuttle (R + 0), or 14 days after landing (R + 14), as well as those of respective control animals. Each group consisted of five male Sprague-Dawley rats. It was demonstrated that T lymphocyte activity of rats dissected in flight was significantly decreased compared with the controls. This was observed during 48-, 72-, and 96-h cultivation and stimulation with the following mitogenic stimuli: concanavalin A (Con A; 0.1, 1.0, and 10.0 mg/ml), phytohemagglutinin (PHA; 2.5 mg/ml), and interleukin-2 (IL-2; 1 U/ml). The cell proliferation rate in rats dissected immediately after landing did not decrease, whereas that in rats dissected at R + 14 increased. The activity of spleen natural killer cells was reduced in response to 51Cr-labeled target cells during flight (YAC-1 and K-562) and after flight (YAC-1). At R + 14, their activity returned to normal. Another technique employed to measure natural cytotoxicity, using [3H]uridine-labeled target cells and ribonuclease, did not reveal any differences between control and experimental groups. In bone marrow, the activity of natural killer cells did not vary significantly. The production of IL-1, IL-2, tumor necrosis factor (TNF)-alpha, and TNF-beta in spleen cell cultures of the flight rats was reduced. At R + 0, IL-1 and TNF-beta levels remained lowered, whereas TNF-alpha was increased. At R + 0, interferon-alpha and interferon-gamma levels were diminished. In summary, cell-mediated immunity in rats was significantly suppressed during flight. The time course variation of immune parameters after flight suggests that the changes may truly indicate a response of the immune system to spaceflight conditions that could increase over time.

Over the past two decades, it has become apparent that changes in immune parameters occur in cosmonauts and astronauts after spaceflight. Therefore, interest has been generated in the use of animal surrogates to better understand the nature and extent of these changes, the mechanism of these changes, and to allow the possible development of countermeasures. Among the changes noted in animals after spaceflight are alterations in lymphocytic blastogenesis, cytokine function, natural killer cell activity, and colony-stimulating factors. The nature and significance of spaceflight-induced changes in immune responses will be the focus of this review.

The effects of spaceflight on immune cell function were determined in rats flown on COSMOS 2044. Control groups included vivarium, synchronous, and antiorthostatically suspended rats. The ability of natural killer cells to lyse two different target cell lines was determined. Spleen and bone marrow cells obtained from flight rats showed significantly inhibited cytotoxicity for YAC-1 target cells compared with cells from synchronous control rats. This could have been due to exposure of the rats to microgravity. Antiorthostatic suspension did not affect the level of cytotoxicity from spleen cells of suspended rats for YAC-1 cells. On the other hand, cells from rats flown in space showed no significant differences from vivarium and synchronous control rats in cytotoxicity for K-562 target cells. Binding of natural killer cells to K-562 target cells was unaffected by spaceflight. Antiorthostatic suspension resulted in higher levels of cytotoxicity from spleen cells for 51Cr-labeled K-562 cells. The results indicate differential effects of spaceflight on function of natural killer cells. This shows that spaceflight has selective effects on the immune response.

During a recent flight of a Russian satellite (Cosmos #2229), initial experiments examining the effects of space flight on immunologic responses of rhesus monkeys were performed to gain insight into the effect of space flight on resistance to infection. Experiments were performed on tissue samples taken from the monkeys before and immediately after flight. Additional samples were obtained approximately 1 month after flight for a postflight restraint study. Two types of experiments were carried out throughout this study. The first experiment determined the ability of leukocytes to produce interleukin-1 and to express interleukin-2 receptors. The second experiment examined the responsiveness of rhesus bone marrow cells to recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF). Human reagents that cross-reacted with monkey tissue were utilized for the bulk of the studies. Results from both studies indicated that there were changes in immunologic function attributable to space flight. Interleukin-1 production and the expression of interleukin-2 receptors was decreased after space flight. Bone marrow cells from flight monkeys showed a significant decrease in their response to GM-CSF compared with the response of bone marrow cells from nonflight control monkeys. These results suggest that the rhesus monkey may be a useful surrogate for humans in future studies that examine the effect of space flight on immune response, particularly when conditions do not readily permit human study.