SUPPRESSED PHA ACTIVATION OF T-LYMPHOCYTES IN SIMULATED MICROGRAVITY IS RESTORED BY DIRECT ACTIVATION OF PROTEIN-KINASE-C

Utilizing clinostatic rotating wall vessel (RWV) bioreactors that simu late aspects of microgravity, we found phytohemagglutinin (PHA) respon siveness to be almost completely diminished. Activation marker express ion was significantly reduced in RWV cultures. Furthermore, cytokine s ecretion profiles suggested that monocytes are not as adversely affect ed by simulated microgravity as T cells. Reduced cell-cell and cell-su bstratum interactions may play a role in the loss of PHA responsivenes s because placing peripheral blood mononuclear cells (PBMC) within sma ll collagen beads did partially restore PHA responsiveness. However, a ctivation of purified T cells with cross-linked CD2/CD28 and CD3/CD28 antibody pairs was completely suppressed in the RWV, suggesting a defe ct in signal transduction. Activation of purified T cells with PMA and ionomycin was unaffected by RWV culture. Furthermore, sub-mitogenic d oses of PMA alone that not ionomycin alone restored PHA responsiveness of PBMC in RWV culture. Thus our data indicate that during polyclonal activation the signaling pathways upstream of PKC activation are sens itive to stimulated microgravity.