| Cell density plays a critical role in ex vivo expansion of T cells for adoptive immunotherapy. | |
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MedLine Citation:
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PMID: 20625484 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Qiangzhong Ma; Yawen Wang; Agnes Shuk-Yee Lo; Erica M Gomes; Richard P Junghans |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. Date: 2010-06-30 |
Journal Detail:
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Title: Journal of biomedicine & biotechnology Volume: 2010 ISSN: 1110-7251 ISO Abbreviation: J. Biomed. Biotechnol. Publication Date: 2010 |
Date Detail:
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Created Date: 2010-07-13 Completed Date: 2010-10-20 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101135740 Medline TA: J Biomed Biotechnol Country: United States |
Other Details:
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Languages: eng Pagination: 386545 Citation Subset: IM |
Affiliation:
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Biotherapeutics Development Laboratory, Roger Williams Medical Center, Boston University School of Medicine, Providence, RI 02908, USA. qma@rwmc.org |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Antigens, CD28 / metabolism Apoptosis Autocrine Communication / immunology Catalase / metabolism Cell Count Cell Lineage Cell Proliferation Culture Media, Conditioned Humans Immunotherapy, Adoptive* Lymphocyte Activation / immunology Reactive Oxygen Species / metabolism Solubility T-Lymphocytes / cytology*, enzymology, immunology*, secretion |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD28; 0/Culture Media, Conditioned; 0/Reactive Oxygen Species; EC 1.11.1.6/Catalase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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