Expansion of regulatory T cells from umbilical cord blood and adult peripheral blood CD4+CD25+ T cells
CD4+CD25+ regulatory T cells (Treg), if properly expanded from umbilical cord blood (UCB), may provide a promising immunotherapeutic tool. Our previous data demonstrated that UCB CD4+CD25+ T cells with 4-day stimulation have comparable phenotypes and suppressive function to that of adult peripheral blood (APB) CD4+CD25+ T cells. We further examined whether 2-week culture would achieve higher expansion levels of Tregs. UCB CD4+CD25+ T cells and their APB counterparts were stimulated with anti-CD3/anti-CD28 in the presence of IL-2 or IL-15 for 2 weeks. The cell proliferation and forkhead box P3 (FoxP3) expression were examined. The function of the expanded cells was then investigated by suppressive assay. IL-21 was applied to study whether it counteracts the function of UCB and APB CD4+CD25+ T cells. The results indicate that UCB CD4+CD25+ T cells expanded much better than their APB counterparts. IL-2 was superior to expand UCB and APB Tregs for 2 weeks than IL-15. FoxP3 expression which peaked on Day 10–14 was comparable. Most importantly, expanded UCB Tregs showed greater suppressive function in allogeneic mixed lymphocyte reaction. The addition of IL-21, however, counteracted the suppressive function of expanded UCB and APB Tregs. The results support using UCB as a source of Treg cells.
KeywordsIL-2 IL-15 IL-21 Regulatory T cells FoxP3
We thank all the health volunteers for participating in this study. This study was supported in part by grants from National Science Council of Republic of China: NSC96-2314-B182A-042-MY2 and NSC101-2314-B-182-033 and grants from Chang Gung Memorial Hospital: CMRPG4A0052, CMRPD4A0053, CMRPD1A0172~3, and CMRPD190511~3.
Conflict of interest
The authors declare no financial or commercial conflict of interest.
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