Department of Microbiology and Immunology, Graduate Institute of Basic Medical Science, Chang Gung University, Taoyuan, Taiwan.
Pediatr Allergy Immunol. 2009 Nov;20(7):624-32. doi: 10.1111/j.1399-3038.2008.00843.x. Epub 2009 Feb 28.
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(+) CD25(high) 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-beta (mTGF-beta), and especially Foxp-3 than controls. IL-2/IL-15-stimulated UCB CD4(+) CD25(+) T cells also produced much higher IL-10 and TGF-beta than controls; while IL-2/IL-15-stimulated UCB CD4(+) CD25(-) T cells showed increased TGF-beta, 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.
脐血（UCB）中 CD4(+) CD25(+)调节性 T 细胞的丰富可能有助于减轻 UCB 移植后移植物抗宿主病（GVHD）的严重程度。本研究旨在研究抗 CD3/抗 CD28（CD3/CD28）和外源性白细胞介素（IL）-2 或 IL-15 对 UCB CD4(+) CD25(+)T 细胞表型和抑制功能的影响。与成人相比，UCB 中 CD4(+) CD25(high)和 FoxP3(+)细胞的比例更高。与 IL-2 相比，IL-15 更有效地增强了 CD3/CD28 刺激的 UCB CD4(+) CD25(+)T 细胞的增殖。表型上，IL-2/IL-15 刺激的 UCB CD4(+) CD25(+)T 细胞表达更高水平的 CTLA-4、GITR、膜结合转化生长因子-β（mTGF-β），尤其是 Foxp-3，比对照组更高。IL-2/IL-15 刺激的 UCB CD4(+) CD25(+)T 细胞也产生比对照组更高水平的 IL-10 和 TGF-β；而 IL-2/IL-15 刺激的 UCB CD4(+) CD25(-)T 细胞显示 TGF-β增加，但 IL-10 没有增加。与对照组相比，IL-2/IL-15 培养的 UCB CD4(+) CD25(+)T 细胞对同种异体成人 CD4(+)T 细胞增殖的抑制活性相当，部分通过接触依赖的方式。总之，IL-2/IL-15 刺激的 UCB CD4(+) CD25(+)T 细胞表现出独特的调节性 T 细胞表型和功能特征，可用于减轻 UCB 移植后 GVHD 的严重程度。
