Cell Density Plays a Critical Role in Ex Vivo Expansion of T Cells for Adoptive Immunotherapy
Lo, Agnes Shuk-Yee
Gomes, Erica M.
Junghans, Richard P.
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Citation (published version)Ma, Qiangzhong, Yawen Wang, Agnes Shuk-Yee Lo, Erica M. Gomes, Richard P. Junghans. "Cell Density Plays a Critical Role in Ex Vivo Expansion of T Cells for Adoptive Immunotherapy" Journal of Biomedicine and Biotechnology 2010:386545.
The successful ex vivo expansion of a large numbers of T cells is a prerequisite for adoptive immunotherapy. In this study, we found that cell density had important effects on the process of expansion of T cells in vitro. Resting T cells were activated to expand at high cell density but failed to be activated at low cell density. Activated T cells (ATCs) expanded rapidly at high cell density but underwent apoptosis at low cell density. Our studies indicated that low-cell-density related ATC death is mediated by oxidative stress. Antioxidants N-acetylcysteine, catalase, and albumin suppressed elevated reactive oxygen species (ROS) levels in low-density cultures and protected ATCs from apoptosis. The viability of ATCs at low density was preserved by conditioned medium from high-density cultures of ATCs in which the autocrine survival factor was identified as catalase. We also found that costimulatory signal CD28 increases T cell activation at lower cell density, paralleled by an increase in catalase secretion. Our findings highlight the importance of cell density in T cell activation, proliferation, survival and apoptosis and support the importance of maintaining T cells at high density for their successful expansion in vitro.
RightsCopyright 2010 Qiangzhong Ma et al.