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.
Authors and Affiliations
Department of Hematology & Oncology, University Hospital Regensburg, 93053, Regensburg, Germany
P Hoffmann, R Eder, R Andreesen & M Edinger
Institute of Pathology, University HospitalRegensburg, 93053, Regensburg, Germany
Hoffmann, P., Eder, R., Kunz-Schughart, L. et al. Large scale in vitro expansion of polyclonal human CD4+CD25high regulatory T cells.
Cancer Cell Int4
(Suppl 1), S11 (2004). https://doi.org/10.1186/1475-2867-4-S1-S11