Falkenburg J H, van Luxemburg-Heijs S A, Lim F T, Kanhai H H, Willemze R
Leiden University Hospital, Department of Hematology, The Netherlands.
Ann Hematol. 1996 Apr;72(4):260-4. doi: 10.1007/s002770050169.
Umbilical cord blood (UCB) has been successfully used as an alternative source of hematopoietic stem cells for allogeneic transplantation. A relatively low incidence and severity of graft-versus-host disease (GVHD) following UCB transplants has been reported, and it has been suggested that this may be caused by a low frequency of alloreactive lymphocytes in UCB. Low frequencies of alloreactive T lymphocytes in UCB may allow transplantation across major MHC barriers with an acceptable risk of GVHD. We investigated cytotoxic T-lymphocyte precursor (CTLp) and helper T-lymphocyte precursor (HTLp) frequencies in UCB. Normal frequencies of CTLp and HTLp were measured against 1-2 HLA class I and 0-1 HLA-DR mismatched stimulator cells. Since it has been postulated that due to maternal fetal transfusion during pregnancy, fetal blood lymphocytes may become tolerant for noninherited maternal antigens (NIMA), allowing transplantation over certain HLA barriers, reactivity of 24 umbilical cord blood samples was analyzed against both parents. The median frequencies of CTLp against NIMA with 1 class-I mismatch was 79 per 10(6) nucleated cells (range 16-428) and with 2 class I mismatches 121 (range 33-748). CTLp frequencies against noninherited paternal antigens (NIPA) were not statistically different from those against NIMA, with a median of 115 (range 8-336) and 176 (range 50-725) for 1 or 2 HLA class I mismatches, respectively. HTLp frequencies in UCB against parents with 0 or 1 HLA-DR antigen mismatches were similar with respect to NIMA (median 74, range 43-233 and 88, range 16-777, respectively) and NIPA (median 125, range 18-174, and 110, range 28-350, respectively). In four cases, UCB from two HLA-identical siblings was tested against both parents. A correlation between the frequencies of CTLp and HTLp from HLA-identical individuals was found, illustrating that these frequencies are genetically determined. These results illustrate that UCB contains normal frequencies of CTLp and HTLp against MHC alloantigens.
脐带血（UCB）已成功用作异基因移植的造血干细胞替代来源。据报道，UCB移植后移植物抗宿主病（GVHD）的发生率和严重程度相对较低，有人认为这可能是由于UCB中同种反应性淋巴细胞频率较低所致。UCB中同种反应性T淋巴细胞频率较低可能允许跨越主要MHC屏障进行移植，且GVHD风险可接受。我们研究了UCB中细胞毒性T淋巴细胞前体（CTLp）和辅助性T淋巴细胞前体（HTLp）的频率。针对1 - 2个I类HLA和0 - 1个HLA - DR错配刺激细胞测定了CTLp和HTLp的正常频率。由于据推测，在怀孕期间由于母胎输血，胎儿血淋巴细胞可能对非遗传母体抗原（NIMA）产生耐受，从而允许跨越某些HLA屏障进行移植，因此分析了24份脐带血样本对父母双方的反应性。针对1个I类错配的NIMA的CTLp中位数频率为每10⁶有核细胞79个（范围16 - 428），针对2个I类错配的为121个（范围33 - 748）。针对非遗传父体抗原（NIPA）的CTLp频率与针对NIMA的频率无统计学差异，针对1个或2个I类HLA错配的中位数分别为115个（范围8 - 336）和176个（范围50 - 725）。UCB中针对0个或1个HLA - DR抗原错配的父母的HTLp频率，针对NIMA（中位数分别为74，范围43 - 233和88，范围16 - 777）和NIPA（中位数分别为125，范围18 - 174和110，范围28 - 350）相似。在4例中，对来自两个HLA相同的同胞的UCB进行了针对父母双方的检测。发现来自HLA相同个体的CTLp和HTLp频率之间存在相关性，说明这些频率是由基因决定的。这些结果表明，UCB中针对MHC同种异体抗原的CTLp和HTLp频率正常。
