Hu H, Robertus M, de Jonge N, Gmelig-Meyling F H, van der Meulen A, Schuurman H J, Doornewaard H, van Prooijen H C, de Weger R A
Department of Pathology, University Hospital, Utrecht, The Netherlands.
Transplantation. 1994 Dec 15;58(11):1263-8.
Tolerance to allografted hearts in human recipients has been observed both in clinical situations and in in vitro experiments. To elucidate whether a quantitative change of alloreactive CTL is one of the mechanisms accounting for this graft tolerance, CTL precursor (CTLp) frequencies in the peripheral blood of 10 heart recipients were measured against spleen cells from donors and HLA nonidentical third-party persons. In this longitudinal follow-up study, we showed that the rejection reaction(s) in the grafted heart correlated with CTLp frequencies in samples taken before transplantation against the donor spleen cells, but not with the CTLp frequencies against the spleen cells from the third-party persons. The CTLp frequencies against the spleen cells from donors decreased 4-6 months after transplantation, and remained at a low level afterward. However, the CTLp frequencies against spleen cells from third-party persons in blood samples obtained 1 year after transplantation were not significantly different from those before transplantation. Therefore, we conclude that donor-reactive CTLs are important in rejecting allografted heart. The decrease in donor-specific CTLp after transplantation could explain the donor-specific tolerance. The decrease may be due to homing of the specific CTLp to the graft, or by clonal deletion of the donor-reactive CTL caused by chronic alloantigen stimulation in the presence of immunosuppressive therapies.
在临床情况和体外实验中均观察到人类心脏移植受者对同种异体心脏的耐受性。为了阐明同种反应性CTL的定量变化是否是导致这种移植耐受的机制之一，我们检测了10名心脏移植受者外周血中针对供体和HLA不匹配第三方人员脾细胞的CTL前体（CTLp）频率。在这项纵向随访研究中，我们发现移植心脏中的排斥反应与移植前样本中针对供体脾细胞的CTLp频率相关，但与针对第三方人员脾细胞的CTLp频率无关。针对供体脾细胞的CTLp频率在移植后4 - 6个月下降，并在随后保持在低水平。然而，移植1年后采集的血样中针对第三方人员脾细胞的CTLp频率与移植前无显著差异。因此，我们得出结论，供体反应性CTL在排斥同种异体心脏中起重要作用。移植后供体特异性CTLp的减少可以解释供体特异性耐受。这种减少可能是由于特异性CTLp归巢至移植物，或在免疫抑制治疗存在的情况下，慢性同种抗原刺激导致供体反应性CTL的克隆清除。
