The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
Large-scale in vitro expansion of polyclonal human CD4+CD25high regulatory T cells
Abstract
CD4+CD25+ regulatory T (Treg) cells are pivotal for the maintenance of self-tolerance, and their adoptive transfer gives protection from autoimmune diseases and pathogenic alloresponses after solid organ or bone marrow transplantation in murine model systems. In vitro, human CD4+CD25+ Treg cells display phenotypic and functional characteristics similar to those of murine CD4+CD25+ Treg cells: namely, hyporesponsiveness to T-cell receptor (TCR) stimulation and suppression of CD25- T cells. Thus far, the detailed characterization and potential clinical application of human CD4+CD25+ Treg cells have been hampered by their paucity in peripheral blood and the lack of appropriate expansion protocols. Here we describe the up to 40 000-fold expansion of highly purified human CD4+CD25high T cells in vitro through the use of artificial antigen-presenting cells for repeated stimulation via CD3 and CD28 in the presence of high-dose interleukin 2 (IL-2). Expanded CD4+CD25high T cells were polyclonal, maintained their phenotype, exceeded the suppressive activity of freshly isolated CD4+CD25high T cells, and maintained expression of the lymph node homing receptors L-selectin (CD62L) and CCR7. The ability to rapidly expand human CD4+CD25high Treg cells on a large scale will not only facilitate their further exploration but also accelerate their potential clinical application in T cell–mediated diseases and transplantation medicine.
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Cites
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Cited by
Sakaguchi, S. (2005) · Nature Immunology · doi:10.1038/ni1178 · Cited by 2,669
Hematopoietic Stem-Cell Transplantation
Copelan, E. A. (2006) · New England Journal of Medicine · doi:10.1056/nejmra052638 · Cited by 2,522
Gobert, M., Treilleux, I., Bendriss-Vermare, N., Bachelot, T., Goddard-Leon, S., Arfi, V., Biota, C., Doffin, A. C., Durand, I., Olive, D., et al. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-2360 · Cited by 758
Expansion of Human Regulatory T-Cells From Patients With Type 1 Diabetes
Putnam, A. L., Brusko, T. M., Lee, M. R., Liu, W., Szot, G. L., Ghosh, T., Atkinson, M. A., & Bluestone, J. A. (2009) · Diabetes · doi:10.2337/db08-1168 · Cited by 357
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Metadata
- Authors
- Hoffmann, P., Eder, R., Kunz-Schughart, L. A., Andreesen, R., & Edinger, M.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2004-08-01
- Volume
- 104
- Issue
- 3
- Pages
- 895-903
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2022221509
- Cited by
- 494
- References
- 49
- FWCI
- 15.35
- Type
- journal article
- Language
- en
- Open access
- closed
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