Spaceflight effects on T lymphocyte distribution, function and gene expression

Abstract

The immune system is highly sensitive to stressors present during spaceflight. The major emphasis of this study was on the T lymphocytes in C57BL/6NTac mice after return from a 13-day space shuttle mission (STS-118). Spleens and thymuses from flight animals (FLT) and ground controls similarly housed in animal enclosure modules (AEM) were evaluated within 3-6 h after landing. Phytohemagglutinin-induced splenocyte DNA synthesis was significantly reduced in FLT mice when based on both counts per minute and stimulation indexes (P < 0.05). Flow cytometry showed that CD3(+) T and CD19(+) B cell counts were low in spleens from the FLT group, whereas the number of NK1.1(+) natural killer (NK) cells was increased (P < 0.01 for all three populations vs. AEM). The numerical changes resulted in a low percentage of T cells and high percentage of NK cells in FLT animals (P < 0.05). After activation of spleen cells with anti-CD3 monoclonal antibody, interleukin-2 (IL-2) was decreased, but IL-10, interferon-gamma, and macrophage inflammatory protein-1alpha were increased in FLT mice (P < 0.05). Analysis of cancer-related genes in the thymus showed that the expression of 30 of 84 genes was significantly affected by flight (P < 0.05). Genes that differed from AEM controls by at least 1.5-fold were Birc5, Figf, Grb2, and Tert (upregulated) and Fos, Ifnb1, Itgb3, Mmp9, Myc, Pdgfb, S100a4, Thbs, and Tnf (downregulated). Collectively, the data show that T cell distribution, function, and gene expression are significantly modified shortly after return from the spaceflight environment.

Microarray analysis of spaceflown murine thymus tissue reveals changes in gene expression regulating stress and glucocorticoid receptors

“…FLT animals is consistent with previous findings using murine space-flown thymus as well as rat osteoblasts and heart cells [Liu et al, 2000;Kumei et al, 2002;Gridley et al, 2009]. Similar alterations in gene expression were also observed in other stress-related genes involving the GR heterocomplex.…”

The influence of leptin on the activity of lung lymphocytes under simulated microgravity

“…Furthermore, lymphocytes treated with ConA or a combination of ConA and leptin showed no diVerences in the production of IL-2 or the expression of CD25 and CD71. Thus, the data shown in a previous study (Gridley et al 2009) are in agreement with our observations that both cytokine production and expression of activation markers are decreased under microgravity. Additionally, our study reveals that, under microgravity, leptin is not an eVective potentiator of ConA activation and was unable to stimulate cognate lymphocyte responses, inducing IL-2 production and the expression of the activation markers CD25 and CD71.…”

Effects of Simulated Microgravity on Primary Human NK Cells

“…Spaceflight induces human immune dysfunction accompanied by an accelerated proliferation of pathogenic microbes and may increase the potential risk of infection and malignant transformation in astronauts (Gridley et al, 2009). The effects of spaceflight on the immune system are not caused simply by physical and psychological stress but may also be directly affected by microgravity (Martinelli et al, 2009).…”

“…(2) IFN-c and perforin: IFN-c is a multifunctional cytokine that promotes both adaptive and innate immune responses (Gridley et al, 2009). Studies of flight crews have generally shown that their lymphocytes have diminished IFN-c …”