Immune dysfunction in space: Investigating the effects of the combined exposure to simulated space conditions on T cells

The space environment poses several health risks for astronauts and future space missions foresee extended periods of human presence in space (such as the creation of a permanent base on the Moon, or future missions to Mars). The immune system is one of the many systems affected by the space exposome. This work describes the use of in vitro models for investigating the effects of simulated space conditions on T cell function, in order to elucidate their role in space-induced immune dysfunction. Initially, a Jurkat cell line was used. Activated cells were exposed to ionizing radiation, stress hormone and simulated altered gravity conditions, namely microgravity, Moon gravity and Mars gravity. To understand how these space conditions affect T cell activation, the levels of IL-2 (important cytokine for T cell development and activity) were measured. Jurkat cell lines are good models for assessing T cell response however, since they are an immortalized cell line, the investigation of mechanistic responses is limited. For this, a second in vitro model, constituted of CD4+ T cells extracted from healthy volunteers, was used. These cells were exposed to ionizing radiation, simulated microgravity and stress hormones. A panel of cytokines as well as transcriptomics investigations were performed. The results from both models showed a strong immunosuppression effect of simulated microgravity and stress hormone. Ionizing radiation exposure responses depended on the radiation quality, with different gene expression profiles being present. From the Jurkat cell model, partial gravity exposures showed different impacts of IL-2 levels, suggesting that the response may not be linear to the gravity level, thus future investigations are needed to better understand this modulation effects. CD4+ T cells results showed that simulated microgravity seems to favor Th2 profiles, shown at the cytokine secretion level, but also at the transcriptomic level. Moreover, while the exposure to ionizing radiation showed pro-inflammatory effects, the combination with the other simulated space conditions, particularly simulated microgravity, abrogated this effect, suggesting a complex interaction and alteration of the cells’ radiation response mechanisms. Taken together, the insights from this doctoral work highlight the impact of the space environment on the immune system and provide a basis for future investigations.