The regulatory function of umbilical cord blood CD4+ CD25+ T cells stimulated with anti-CD3/anti-CD28 and exogenous interleukin (IL)-2 or IL-15

The abundance of CD4+ CD25+ regulatory T cells in umbilical cord blood (UCB) might contribute to the decreased severity of graft‐vs.‐host disease (GVHD) for UCB transplantation. This study aims to characterize the phenotypes and suppressive function of UCB CD4+ CD25+ T cells under the influence of anti‐CD3/anti‐CD28 (CD3/CD28) and exogenous interleukin (IL)‐2 or IL‐15. Higher percentages of CD4+ CD25high and FoxP3+ cells were detected in UCB compared to their adult counterparts. IL‐15 was as effective as IL‐2 in enhancing the proliferation of CD3/CD28 stimulated UCB CD4+ CD25+ T cells. Phenotypically, IL‐2/IL‐15‐stimulated UCB CD4+ CD25+ T cells expressed higher level of CTLA‐4, GITR, membrane bound transforming growth factor‐β (mTGF‐β), and especially Foxp‐3 than controls. IL‐2/IL‐15‐stimulated UCB CD4+ CD25+ T cells also produced much higher IL‐10 and TGF‐β than controls; while IL‐2/IL‐15‐stimulated UCB CD4+ CD25− T cells showed increased TGF‐β, but not IL‐10 production. IL‐2/IL‐15‐cultured UCB CD4+ CD25+ T cells showed comparable suppressor activity on allogeneic adult CD4+ T‐cell proliferation compared to controls, partly through a contact‐dependent fashion. Taken together, IL‐2/IL‐15‐stimulated UCB CD4+ CD25+ T cells show distinct regulatory T‐cell phenotypic and functional features, and may be applied for the alleviation of GVHD severity following UCB transplantation.