Gaschet J, Gallot G, Ibisch C, Lim A, Even J, Vivien R, Hallet M M, Milpied N, Vié H
Institut National de la Santé et de la Recherche Médicale Unité 463, Plateau Technique du CHR, Nantes, France.
Bone Marrow Transplant. 1998 Aug;22(4):385-92. doi: 10.1038/sj.bmt.1701336.
HLA-DP incompatibility is not considered as an exclusion criterion for bone marrow donors, because such incompatibility was not shown to affect significantly the risk for acute graft-versus-host disease (GVHD). In line with this clinical observation, it was proposed that in the context of bone marrow transplantation, HLA-DP determinants did not function as transplantation antigens in the same way as HLA-A, -B or -DR. In contrast to the above conclusion, we recently demonstrated the presence of HLA-DPB10501 specific T cell clones in a skin biopsy of a patient who developed aGVHD after receiving a bone marrow transplant (BMT) in which the only mismatched allele in the GVHD direction was HLA-DPB10501. At that time, this case was unique and occurred in a relatively uncommon graft setting where the patient received purified CD34+ BM cells from an unrelated donor. In the present study, we analyzed the immunological events associated with an aGVHD which occurred in the context of a 'regular' allogeneic BMT involving a single HLA-DPB11001 mismatch between donor and recipient in the GVHD direction. To this end, we analyzed several amplified T cell subsets present within a T cell line derived from a skin biopsy performed at the onset of GVHD. Our results demonstrated that T cell populations belonging to the TCRBV2, TCRB6.7, TCRBV14 and TCRBV17 subsets were specific for the HLA-DPB11001 mismatched allele. These data strengthen and generalize our first conclusion that a single HLA-DP mismatch between donor and recipient can activate a strong T cell response in vivo and consequently challenge the notion that HLA-DP incompatibility should not be taken into account in the choice of BM donors. Moreover, they also underline the idea that HLA-DP antigens may represent an interesting immune target for future therapeutic approaches.
HLA - DP不相容性不被视为骨髓供体的排除标准，因为尚未表明这种不相容性会显著影响急性移植物抗宿主病（GVHD）的风险。与这一临床观察结果一致，有人提出在骨髓移植的背景下，HLA - DP决定簇不像HLA - A、- B或 - DR那样作为移植抗原发挥作用。与上述结论相反，我们最近在一名接受骨髓移植（BMT）后发生急性移植物抗宿主病（aGVHD）的患者的皮肤活检中发现了HLA - DPB10501特异性T细胞克隆，在该移植中，移植物抗宿主病方向上唯一不匹配的等位基因是HLA - DPB10501。当时，这个病例是独一无二的，发生在一种相对不常见的移植情况下，即患者接受了来自无关供体的纯化CD34 +骨髓细胞。在本研究中，我们分析了与在“常规”同种异体骨髓移植背景下发生的急性移植物抗宿主病相关的免疫事件，该移植在移植物抗宿主病方向上供体和受体之间存在单个HLA - DPB11001不匹配。为此，我们分析了在急性移植物抗宿主病发作时从皮肤活检中获得的T细胞系中存在的几个扩增的T细胞亚群。我们的结果表明，属于TCRBV2、TCRB6.7、TCRBV14和TCRBV17亚群的T细胞群体对HLA - DPB11001不匹配等位基因具有特异性。这些数据强化并推广了我们的第一个结论，即供体和受体之间单个HLA - DP不匹配可在体内激活强烈的T细胞反应，因此对在选择骨髓供体时不应考虑HLA - DP不相容性这一观点提出了挑战。此外，它们还强调了HLA - DP抗原可能代表未来治疗方法中一个有趣的免疫靶点这一观点。
