Sub-mitogenic phorbol myristate acetate co-stimulation rescues the PHA-induced activation of both naïve and memory T cells cultured in the rotating-wall vessel bioreactor.
T lymphocytes are unresponsive to T cell receptor (TCR) stimulation during culture in spaceflight or ground-based microgravity analogs such as the rotating-wall vessel (RWV) bioreactor. The TCR-induced activation of a subset of T cells can be rescued in the RWV by co-stimulation with sub-mitogenic doses of phorbol ester (PMA). We report that PMA co-stimulation of primary human T cells cultured in the RWV rescues the phytohemagglutinin (PHA)-induced activation of the CD8+ and CD4+ T cell subsets as well as naïve and memory CD4+ T cells. Importantly, T cells activated in the RWV by PHA+PMA contained these subsets in proportions strikingly similar to control cultures activated with PHA alone. The data indicate that rescuing T cell activation with PMA co-stimulation does not significantly perturb the heterogeneity of the responding cells, and represent an important proof of principle for the design of immune-boosting agents for use in spaceflight.
Simons
Donald M
DM
School of Biomedical Engineering, Science and Health Systems, Drexel University, 3141 Chestnut St., Bossone Bldg. Rm. 707, Philadelphia, PA 19104, USA.
Gardner
Elizabeth M
EM
Lelkes
Peter I
PI
D019149:Bioreactors; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D010835:Phytohemagglutinins / Q000494:pharmacology*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D018474:Weightlessness Simulation
D010835:Phytohemagglutinins; D011948:Receptors, Antigen, T-Cell; D013755:Tetradecanoylphorbol Acetate