Roncarolo M G, Yssel H, Touraine J L, Bacchetta R, Gebuhrer L, De Vries J E, Spits H
UNICET, Laboratories for Immunological Research, Dardilly, France.
J Exp Med. 1988 Dec 1;168(6):2139-52. doi: 10.1084/jem.168.6.2139.
Tetanus toxin (TT)-specific T cell clones of donor origin were obtained from a patient with severe combined immunodeficiency (SCID) successfully reconstituted by transplantation of allogeneic fetal liver and thymus cells from two different donors performed 10 yr ago. A series of these clones recognized TT in the context of "allo" class II HLA determinants expressed by recipient APC. The restriction element of two T cell clones with the HLA phenotype of the first donor (HLA-DR1,8) and one T cell clone with the HLA phenotype of the second transplant (HLA-DR3,9) was HLA-DR4 of the recipient, whereas other T cell clones derived from the second transplant recognized TT in the context of HLA-DR5 of the recipient's APC. These latter T cell clones were not able to proliferate in response to TT when autologous APC were used. These data demonstrate that recipient and donor cells having different HLA phenotypes could cooperate across the allogeneic barrier and that MHC restriction of antigen (Ag) recognition is independent from the MHC genotype of the T cells but is influenced by the environment in which the T cells mature. We also isolated T cell clones that were able to recognize processed TT presented by all allogeneic EBV cell lines tested, indicating that the Ag specificity of these clones was not restricted by a particular class II MHC molecule. The Ag-specific proliferative response of one of these clones could be blocked by anti-class II MHC mAbs. These results demonstrate that in addition to Ag recognition in the context of specific class II MHC Ags, other types of Ag-specific responses may occur in this human chimera. It is not clear whether this "allo" plus Ag recognition is the result of education of transplanted fetal cells in the host thymus. Taking into consideration our previous findings indicating that alloreactive T cell clones specific for the recipient cells could be isolated in vitro from the PBL of the same patient, our data suggest that the mechanism for deletion of self-reactive clones and the generation of MHC-restricted responses are different.
破伤风毒素（TT）特异性供体来源的T细胞克隆，取自一名严重联合免疫缺陷（SCID）患者，该患者于10年前成功接受了来自两名不同供体的异基因胎儿肝脏和胸腺细胞移植。一系列这些克隆在受体抗原呈递细胞（APC）表达的“allo”II类HLA决定簇的背景下识别TT。两个具有第一供体HLA表型（HLA - DR1,8）的T细胞克隆和一个具有第二次移植HLA表型（HLA - DR3,9）的T细胞克隆的限制元件是受体的HLA - DR4，而其他源自第二次移植的T细胞克隆在受体APC的HLA - DR5背景下识别TT。当使用自体APC时，这些后一种T细胞克隆不能对TT产生增殖反应。这些数据表明，具有不同HLA表型的受体和供体细胞可以跨越同种异体屏障进行协作，并且抗原（Ag）识别的MHC限制独立于T细胞的MHC基因型，但受T细胞成熟环境的影响。我们还分离出了能够识别所测试的所有异基因EBV细胞系呈递的加工后TT的T细胞克隆，表明这些克隆的Ag特异性不受特定II类MHC分子的限制。这些克隆之一的Ag特异性增殖反应可被抗II类MHC单克隆抗体阻断。这些结果表明，除了在特定II类MHC Ags背景下的Ag识别外，在这种人嵌合体中可能还会发生其他类型的Ag特异性反应。尚不清楚这种“allo”加Ag识别是否是宿主胸腺中移植胎儿细胞受教育的结果。考虑到我们之前的发现，即可以从同一患者的外周血淋巴细胞（PBL）中体外分离出对受体细胞具有同种异体反应性的T细胞克隆，我们的数据表明，自身反应性克隆的缺失机制和MHC限制反应的产生机制是不同的。
