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.

Fig. 1.

Stimulation index (SI) for splenocytes after activation with phytohemagglutinin (PHA). Data were obtained using [³H]thymidine incorporation. AEM, animal enclosure modules; FLT, flight animals. SI = (cpm with mitogen − cpm without mitogen)/cpm without mitogen, where cpm is counts per minute. Bars represent means ± SE (n = 12 mice/group).

Fig. 2.

Lymphocyte populations in the spleen. Data were obtained using fluorescence-labeled monoclonal antibodies and flow cytometry. Th, T helper cells; Tc, T cytotoxic cells; NK, natural killer cells. Bars represent means ± SE (n = 12 mice/group).

Fig. 3.

Cytokine levels after splenocyte activation with anti-CD3 monoclonal antibody. Cytokines in spleen cell supernatants were quantified by ELISA. MIP-1α, macrophage inflammatory protein-1α. Bars represent means ± SE (n = 12 mice/group).