CD4+CD25+ regulatory T (Treg) cells are pivotal for the maintenance of self-tolerance and their adoptive transfer protects 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 similar phenotypic and functional characteristics as murine CD4+CD25+ Treg cells, namely hyporesponsiveness to TCR stimulation and suppression of CD25- T cells. Thus far, the detailed characterization and potential clinical application of human CD4+CD25+ Treg cells was 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 APC for repeated stimulation via CD3 and CD28 in the presence of high dose IL-2. Expanded CD4+CD25high T cells were polyclonal, maintained their phenotype, exceeded the suppressive activity of freshly isolated CD4+CD25high T cells and showed characteristics of central memory T cells. The ability to rapidly expand human CD4+CD25high Treg cells large scale will not only facilitate their further exploration but also accelerate their potential clinical application in T cell-mediated diseases and transplantation medicine.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
This article is published under an open access license. Please check the 'Copyright Information' section either on this page or in the PDF for details of this license and what re-use is permitted. If your intended use exceeds what is permitted by the license or if you are unable to locate the licence and re-use information, please contact the Rights and Permissions team.
About this article
Cite this article
Hoffmann, P., Eder, R., Kunz-Schughart, L. et al. Large scale in vitro expansion of polyclonal human CD4+CD25high regulatory T cells. Cancer Cell Int 4 (Suppl 1), S11 (2004). https://doi.org/10.1186/1475-2867-4-S1-S11
Received:
Published:
DOI: https://doi.org/10.1186/1475-2867-4-S1-S11