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Microgravity-Induced Changes in Gene Expression in Activated T-lymphocytes Involve Multiple Regulatory Pathways.    N. E. Ward1, N. R. Pellis2, S. A. Risin3 and D. Risin2     1Wyle Life Sciences, Houston, TX, 2NASA,  Johnson Space Center, Houston, TX and 3University of Texas-Houston Medical School.

   We and others have shown that exposure to microgravity (MG) results in a decline in cellular immune function.  To further investigate this phenomenon, microarray analysis was employed to identify associated gene expression changes and possible gravity sensitive genes.  CD3- and IL2-activated T-cells were cultured in 1g (static) and modeled microgravity (Rotating Wall Vessel bioreactor) conditions for 24 hours. Microarray experiments were performed utilizing Affymetrix Gene Chips. To decrease biological variation and aid in detecting microgravity-associated changes, experiments were performed in triplicate utilizing T-cells obtained from different blood donors. Exposure to modeled microgravity resulted in alteration of 89 genes, 10 of which were up-regulated and 79 down-regulated. Up-regulated genes included IL7-receptor which plays a role in lymphocyte development, and several heat shock protein family members which function together as molecular chaperones.  Down-regulated genes included granzyme B, beta-3-endonexin, and Apo-2 ligand, all three of which have various roles in the induction of apoptosis.  Also down-regulated were three proteasome beta family members, several genes potentially affecting the integrity of the cellular cytoskeleton such as CD2 associated protein, tubulin, and pericentrin 1, genes affecting DNA repair such as nudix and FEN1, and genes affecting several metabolic pathways such as glucose 6-phosphate dehydrogenase in the pentose phosphate pathway.  These data provide base information and a means to evaluate the possible roles of genes demonstrating altered expression in lymphocyte response to microgravity at the molecular level.  (Supported by NRA OLMSA-02 and NSCORT NAG5-4072 grants).