Kloosterboer F M, van Luxemburg-Heijs S A P, Willemze R, Falkenburg J H F
Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands.
Hum Immunol. 2006 Nov;67(11):874-83. doi: 10.1016/j.humimm.2006.02.040. Epub 2006 Aug 28.
Low alloreactivity of umbilical cord blood (UCB) T-cells may explain diminished graft-versus-host-disease after UCB transplantation. We investigated whether UCB T-cells have an intrinsic lower capacity to become activated. T-cells from UCB or adult blood (AB) were stimulated with anti-CD3 and anti-CD28 antibodies. On days 1-3 after stimulation, T-cell activation was determined by CD25 expression, proliferation was measured, and kinetics of cell division were analyzed by staining with CFSE. UCB and AB T cells exhibited similar numbers of activated and proliferating cells, but the extent of activation was lower in UCB T-cells. Enzyme-linked immunospot analysis showed lower levels and slower kinetics of IL-2, IL-4, IL-10, and IFN-gamma secreting cells for UCB T-cells. Comparison of UCB T-cells with CD45RA+ naive or CD45RO+ memory T cells purified from AB showed relatively low numbers of IL-4 and IL-10 secreting T cells in CD45RA+ AB T-cells and UCB T-cells as compared with CD45RO+ AB T cells. Numbers of IL-2 or IFN-gamma secreting cells in adult CD45RA+ T-cells were lower than in CD45RO+ T-cells but higher than in UCB T-cells. Thus diminished reactivity of UCB T-cells was not caused by a lower capacity to become activated and proliferate but may be explained by a lower extent of activation in UCB T cells, the absence of memory T cells in UCB, and differences between naive T cells from UCB and AB.
脐带血(UCB)T细胞的低同种异体反应性可能解释了UCB移植后移植物抗宿主病减轻的原因。我们研究了UCB T细胞是否具有内在的较低激活能力。用抗CD3和抗CD28抗体刺激来自UCB或成人血液(AB)的T细胞。在刺激后的第1 - 3天,通过CD25表达确定T细胞激活情况,测量增殖情况,并通过CFSE染色分析细胞分裂动力学。UCB和AB T细胞表现出相似数量的激活和增殖细胞,但UCB T细胞的激活程度较低。酶联免疫斑点分析显示,UCB T细胞分泌IL - 2、IL - 4、IL - 10和IFN - γ的细胞水平较低且动力学较慢。将UCB T细胞与从AB中纯化的CD45RA + 初始或CD45RO + 记忆T细胞进行比较,结果显示与CD45RO + AB T细胞相比,CD45RA + AB T细胞和UCB T细胞中分泌IL - 4和IL - 10的T细胞数量相对较少。成人CD45RA + T细胞中分泌IL - 2或IFN - γ的细胞数量低于CD45RO + T细胞,但高于UCB T细胞。因此,UCB T细胞反应性降低不是由于激活和增殖能力较低,而是可能由UCB T细胞激活程度较低、UCB中缺乏记忆T细胞以及UCB和AB初始T细胞之间的差异所解释。