Liu Yin Ping, Li Zengqi, Nador Roland G, Strober Samuel
Division of Immunology & Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305-5166, USA.
Transplantation. 2008 Feb 27;85(4):607-14. doi: 10.1097/TP.0b013e31816361ce.
The use of combined organ and bone marrow transplantation has been studied extensively in rodent models to induce immune tolerance to organ grafts. However, bone marrow transplants with mature donor T cells can induce graft-versus-host disease even in human leukocyte antigen-matched humans. We determined whether total lymphoid irradiation can simultaneously protect against graft-versus-host disease while facilitating tolerance.
To more closely model clinical studies, we added mature donor T cells to bone marrow grafts combined with heart grafts, and compared murine graft and host survival after conditioning with nonmyeloablative total body or total lymphoid irradiation and depletive anti-T-cell antibodies.
Conditioning with total lymphoid irradiation protected hosts against both graft-versus-host disease and organ graft rejection. Although nonmyeloblative total body irradiation prevented organ graft rejection, all hosts succumbed to lethal graft-versus host disease. Induction of tolerance with total lymphoid irradiation and anti-T-cell antibodies was dependent on the presence of regulatory host natural killer T cells, and expression of CD1d on donor marrow but not heart graft cells.
Conditioning with total lymphoid irradiation and anti-T-cell antibodies prevented host-versus-donor and donor-versus-host alloimmune responses. Tolerance required host natural killer T-cell recognition of CD1d on donor marrow cells.
在啮齿动物模型中，联合器官与骨髓移植已被广泛研究，以诱导对器官移植的免疫耐受。然而，即使在人类白细胞抗原匹配的个体中，含有成熟供体T细胞的骨髓移植也可诱发移植物抗宿主病。我们研究了全身淋巴照射是否能在促进耐受的同时预防移植物抗宿主病。
为了更贴近临床研究，我们将成熟供体T细胞添加到与心脏移植相结合的骨髓移植中，并比较了在采用非清髓性全身照射或全身淋巴照射及去除性抗T细胞抗体进行预处理后小鼠移植物和宿主的存活情况。
全身淋巴照射预处理可保护宿主免受移植物抗宿主病和器官移植排斥反应。虽然非清髓性全身照射可预防器官移植排斥反应，但所有宿主均死于致死性移植物抗宿主病。全身淋巴照射和抗T细胞抗体诱导的耐受依赖于调节性宿主自然杀伤T细胞的存在，以及供体骨髓而非心脏移植细胞上CD1d的表达。
全身淋巴照射和抗T细胞抗体预处理可预防宿主抗供体和供体抗宿主同种免疫反应。耐受需要宿主自然杀伤T细胞识别供体骨髓细胞上的CD1d。
