de Haan A, van den Berg A P, Hepkema B G, van Dijk E, Haagsma E B, The T H, Slooff M J, Lems S P, de Leij L F, Prop J
Department of Cardiopulmonary Surgery, University Hospital Groningen, The Netherlands.
Transplantation. 1998 Aug 27;66(4):516-22. doi: 10.1097/00007890-199808270-00017.
The development of immunological donor-specific hyporeactivity may account for the low incidence of chronic rejection after clinical liver transplantation. We investigated whether hyporeactivity commonly develops after liver transplantation by analyzing precursor frequencies of donor-reactive cytotoxic (CTLp) and helper (HTLp) T lymphocytes and mixed lymphocyte culture (MLC) reactivity in liver allograft recipients. We further studied whether CTLp hyporeactivity correlated with changes in donor-specific HTLp frequencies or suppressor cell activity.
CTLp and HTLp frequencies and MLC reactivity against donor and third-party spleen cells were determined in pre- and posttransplantation peripheral blood samples from 18 recipients with good graft function 2 years after transplantation. By mixing posttransplantation samples (with "putative" suppressor cell activity) with pretransplantation samples (in which normal CTL activity with no suppressor cell activity is expected), the presence of suppressor cell activity in peripheral blood was analyzed.
Two years after transplantation, all but one (94%) of the recipients had developed CTLp hyporeactivity as evidenced by reduced donor-specific CTLp frequencies. The development of hyporeactivity was not specific for any particular underlying disease. The occurrence of HTL hyporeactivity, however, was less frequent: 38% and 20% of recipients were HTLp and MLC hyporeactive, respectively. Decreases in CTLp frequencies did not correlate with decreased donor-specific HTL function or suppressor cell activity in peripheral blood samples.
Donor-specific CTLp hyporeactivity can develop in the majority of liver allograft recipients, irrespective of underlying disease. Donor-specific HTL hyporeactivity, however, occurs infrequently. A reduction in donor-specific CTLp frequencies was found to be independent of changes in donor-specific HTLp or suppressor cell activity, suggesting that other mechanisms (e.g., clonal deletion) are operative in the reduction of donor-specific CTLp after liver transplantation.
免疫性供体特异性低反应性的形成可能是临床肝移植后慢性排斥反应发生率低的原因。我们通过分析肝移植受者中供体反应性细胞毒性（CTLp）和辅助性（HTLp）T淋巴细胞的前体频率以及混合淋巴细胞培养（MLC）反应性，来研究肝移植后低反应性是否普遍形成。我们进一步研究了CTLp低反应性是否与供体特异性HTLp频率的变化或抑制细胞活性相关。
测定了18例移植后2年移植物功能良好的受者移植前后外周血样本中CTLp和HTLp频率以及针对供体和第三方脾细胞的MLC反应性。通过将移植后的样本（具有“假定”抑制细胞活性）与移植前的样本（预期具有正常CTL活性且无抑制细胞活性）混合，分析外周血中抑制细胞活性的存在情况。
移植后2年，除1例（94%）外，所有受者均出现了CTLp低反应性，表现为供体特异性CTLp频率降低。低反应性的形成并非特定于任何特定的基础疾病。然而，HTL低反应性的发生频率较低：分别有38%和20%的受者为HTLp低反应性和MLC低反应性。外周血样本中CTLp频率的降低与供体特异性HTL功能的降低或抑制细胞活性无关。
大多数肝移植受者均可出现供体特异性CTLp低反应性，与基础疾病无关。然而，供体特异性HTL低反应性很少发生。发现供体特异性CTLp频率的降低与供体特异性HTLp或抑制细胞活性的变化无关，这表明在肝移植后供体特异性CTLp减少的过程中存在其他机制（如克隆清除）。
