Editorial: Space flight modifies T cell activation—role of microgravity

Exposure of organisms or cells to spaceflight conditions has resulted in perturbations of immune responses [1–3]. Changes in the immune responses of humans, animals, and cell cultures have been observed [1–3]. Although cell-mediated immunity has been shown to be primarily affected, alterations in humoral immune responses after spaceflight have also been observed [1–3]. Both the natural and adaptive immune systems were affected [1–3]. Altered functions include cytokine production, leukocyte blastogenesis, NK cell and macrophage activity and production, antibody production, and enzyme functions in pathways important for immune functions [1–3]. The latest studies have indicated changes in in neutrophil, monocyte, and lymphocyte populations (cell population numbers and function), hypoplasia of lymphoid organs, altered expression of antibody variable heavy chain genes, and others in response to spaceflight conditions [4]. Although effects of the spaceflight environment on the immune system have been established for some time, two important questions have remained unanswered over time. The first is: what is the functional significance of the immune system changes that occur after spaceflight? The second is: what in the spaceflight environment is causing the changes observed in the immune system? The functional significance of changes in immune responses remains to be answered. The immune response changes that occur during spaceflight could result in altered resistance to infection or cancer or to altered hypersensitivity reactions, yielding severe clinical manifestations that could endanger the host [1–3]. For the most part, this has not occurred in the spaceflights carried out to date [1–3]. As very long-term flights into space, including missions to Mars, are contemplated, however, this situation may change. Alterations in immune function, coupled with changes in growth patterns and expression of virulence factors induced by spaceflight [5], could result in increased risk of infection or cancer, as the duration of spaceflight increases, and return to earth for treatment becomes impossible. This should be the subject of future studies, and these studies will be required prior to the commencement of deep space exploration. The study by Chang et al. [6] addresses the second question. The cause(s) of the alterations in immune function induced by exposure to spaceflight conditions have not been established. There are multiple variables encountered in the exposure of humans, animals, and cells to spaceflight conditions [1–4]. These include: microgravity (very reduced gravity experienced in low earth orbit spaceflights), stress (including landing), vibration, alterations in pressure and ambient temperature, radiation, changes in sheer forces, as well as other variables that may not, as yet, have been identified [1–4] (Fig. 1). These variables could each individually affect immune system function. Additionally, the variables could be interactive in the spaceflight environment to affect immune function in a way that does not normally happen on earth [1– 4]. Hence, the question of which variable or variables are responsible for spaceflight-induced alterations in immune function had to be answered. In the current study, human T cells were stimulated with Con A and antiCD28 on board of the ISS to induce immune responses [6]. Microarray expression analysis after 1.5 h of activation demonstrated that the T cells activated in microgravity (during flight on the ISS) had distinct patterns of global gene expression that differed from those activated in a 1-g centrifuge during spaceflight (controlfor normal gravity that can be run during spaceflight) [6]. Forty-seven genes were identified that were significantly differentially down-regulated in T cells exposed to microgravity compared with T cells exposed to microgravity in a 1-g centrifuge [5]. Activation of Rel/NFB, CREB, and serum response factor gene targets, genes important in immune cell function pathways, was down-regulated [6]. These data suggest that the TNF pathway is a major early downstream effector pathway inhibited in microgravity, and this could lead to ineffective, proinflammatory host defenses against infections during long-term spaceflight. These results may suggest that there could be a direct effect of microgravity on the expression of genes controlling immune cell function [1–4, 6]. Although several experiments have been carried out in the past to attempt to show a direct