Roncarolo M G, Touraine J L, Banchereau J
J Clin Invest. 1986 Mar;77(3):673-80. doi: 10.1172/JCI112361.
Fetal liver and thymus transplantation can be successfully employed for the treatment of severe combined immunodeficiency disease. In virtually all cases, donor and recipient cells are HLA mismatched. In a patient suffering from a severe combined immunodeficiency disease, full immunological reconstitution was obtained after fetal liver and thymus transplantation. HLA typing revealed that the patient's T cells were of donor origin, while the B cells and monocytes were of host origin. Despite this complete HLA mismatch, the patient was found to mount a subnormal to normal antibody response in vivo. This finding is in contrast with the concept that antigen recognition by T cells is major histocompatibility complex (MHC) restricted. To define the mechanism responsible for this in vivo antibody response, antibody production by peripheral blood mononuclear cells from the patient was tested in vitro after in vivo booster. The in vitro anti-tetanus toxoid antibody production was similar to that of the control group. In addition, specific proliferative responses to tetanus toxoid were obtained. Immunoglobulin allotype determination showed that antibodies were synthetized by host B cells. The results of the present study indicate that transplanted T lymphocytes and recipient cells cooperate despite complete HLA mismatch.
胎儿肝脏和胸腺移植可成功用于治疗严重联合免疫缺陷病。实际上在所有病例中,供体和受体细胞的人类白细胞抗原(HLA)均不匹配。在一名患有严重联合免疫缺陷病的患者中,胎儿肝脏和胸腺移植后获得了完全的免疫重建。HLA分型显示患者的T细胞来源于供体,而B细胞和单核细胞来源于宿主。尽管HLA完全不匹配,但发现该患者在体内产生的抗体反应从低于正常水平到正常水平。这一发现与T细胞对抗原的识别受主要组织相容性复合体(MHC)限制这一概念相反。为了确定体内抗体反应的机制,在体内加强免疫后,对患者外周血单个核细胞的抗体产生进行了体外检测。体外抗破伤风类毒素抗体的产生与对照组相似。此外,还获得了对破伤风类毒素的特异性增殖反应。免疫球蛋白同种异型测定表明抗体是由宿主B细胞合成的。本研究结果表明,尽管HLA完全不匹配,移植的T淋巴细胞与受体细胞仍能协同作用。