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J Appl Physiol 100: 1287-1292, 2006. First published December 29, 2005; doi:10.1152/japplphysiol.00887.2005
8750-7587/06 $8.00
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TRANSLATIONAL PHYSIOLOGY

Dynamic culture in a rotating-wall vessel bioreactor differentially inhibits murine T-lymphocyte activation by mitogenic stimuli upon return to static conditions in a time-dependent manner

D. M. Simons,1 E. M. Gardner,2 and P. I. Lelkes1

1School of Biomedical Engineering, Science, and Health Systems and 2Department of Bioscience and Biotechnology, Drexel University, Philadelphia, Pennsylvania

Submitted 22 July 2005 ; accepted in final form 5 December 2005

ABSTRACT

Depressed immune function is a well-documented effect of spaceflight. Both in-flight studies and ground-based studies using microgravity analogs, such as rotating wall vessel (RWV) bioreactors, have demonstrated that mitogen-stimulated T lymphocytes exhibit decreased proliferation, IL-2 secretion, and activation marker expression in true microgravity and the dynamic RWV-culture environment. This study investigates the kinetics of RWV-induced T lymphocyte inhibition by monitoring the ability of Balb/c mouse splenocytes to become activated under static culture conditions after concanavalin A (Con A) stimulation in an RWV. Splenocytes were stimulated with Con A and cultured for up to 24 h in the RWV before being allowed to "recover" under static culture conditions in the continued presence of Con A. The T-lymphocyte fraction of splenocytes was assayed during the recovery period for IL-2 secretion, expansion of the T-lymphocyte population, and expression of the activation marker CD25. Our results indicate that CD25 expression was not affected by any duration of RWV exposure. In contrast, proliferation and IL-2 secretion were inhibited by >8 and 12 h of exposure, respectively. Culture in the RWV for 24 h resulted in a near-complete loss of cellular viability during the recovery period, which was not seen in cells maintained in the RWV for 16 h or less. Taken together, these results indicate that for up to 8 h of RWV culture activation is not significantly impaired upon return to static conditions; longer duration RWV culture results in a gradual loss of activation during the recovery period most likely because of decreased T-cell viability and/or IL-2 production.

microgravity; immune response; spaceflight



Address for reprint requests and other correspondence: P. I. Lelkes, Drexel Univ. School of Biomedical Engineering, Science, and Health Systems, Commonwealth Hall 7-721, 3142 Chestnut St., Philadelphia, PA 19104 (e-mail: pilelkes{at}drexel.edu)







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