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Journal of Biomedicine and Biotechnology
Volume 2010, Article ID 386545, 13 pages
http://dx.doi.org/10.1155/2010/386545
Research Article

Cell Density Plays a Critical Role in Ex Vivo Expansion of T Cells for Adoptive Immunotherapy

1Biotherapeutics Development Laboratory, Roger Williams Medical Center, Boston University School of Medicine, Providence, RI 02908, USA
2Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA

Received 24 December 2009; Revised 5 April 2010; Accepted 6 May 2010

Academic Editor: Zhengguo Xiao

Copyright © 2010 Qiangzhong Ma et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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.