PATHOGENESIS OF GRAFT-VERSUS-HOST REACTIONS (GVHR) AND GVH-LIKE DISEASES
PATHOGENESIS OF GRAFT-VERSUS-HOST REACTIONS (GVHR) AND GVH-LIKE DISEASES
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DOI：
10.1111/1523-1747.ep12275619
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发表时间：
1985-01-01
影响因子：
6.5
通讯作者：
GLEICHMANN, H
中科院分区：
文献类型：
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作者：
GLEICHMANN, E;GLEICHMANN, H
小鼠和人类的移植物抗宿主反应(GVHR)可导致广泛的临床和病理症状的发展。这些症状与一些已证实或推测为免疫学原因的疾病，如系统性红斑狼疮(SLE)、其他胶原血管疾病、淋巴增生性疾病和再生障碍性贫血的症状惊人地相似。我们研究的目的是描述移植物抗宿主病(GVHD)过程中发生的免疫学和病理学事件，并深入了解这些事件背后的细胞机制。为此，采用了一种模型，在该模型中，未经照射的F1小鼠被用作亲代淋巴样细胞的受体。根据病理表现，在这些未经照射的F1受体中，GVHD可区分为两种基本形式：一种是急性GVHD，通常是致命的。它的特点是各种抑制性(发育不良)的病理症状，包括严重的淋巴造血系统发育不良伴发再生障碍性贫血和低丙种球蛋白血症。另一种基本类型以刺激性症状为特征，如持续性淋巴组织增生、自身抗体的形成以及类似于SLE和其他胶原血管疾病的病理症状的发展。抑制性病理性移植物抗宿主(GVH)症状是由供者的T抑制/杀伤(TS/K)细胞对F1受体的主要组织相容性复合体(MHC)的同种异体I类结构反应引起的。相反，刺激性病理性GVH症状是由供者的T辅助细胞(TH)引起的，TH细胞对受者的同种异体II-MHC结构起反应。这些观察结果可能对人类GVH样疾病的发病机制产生影响。提出的假说是，这些类似GVH的情况，无论是暴露于某些病毒或药物后的原因，都是由T淋巴细胞与淋巴造血细胞上的自身MHC结构发生反应引起的，而淋巴造血细胞上的自身MHC结构被变为“异物”。通过与GVHD的类比，可以想象，在暴露于特定病毒或致敏药物的个人中，无论是刺激性还是抑制性的GHV样症状的发展不取决于病原学本身，而是取决于个人的Thors/K细胞是否做出了先兆反应。反过来，这可能取决于该试剂是否与II类或I类同种异体抗原结合成为免疫原性。
The graft-versus-host reaction (GVHR) in both mice and humans can lead to the development of a broad spectrum of clinical and pathological symptoms. These symptoms are strikingly similar to those of a number of diseases of proven or presumed immunological origin, such as systemic lupus erythematosus (SLE), other collagen vascular diseases, lymphoproliferative disease, and aplastic anemia.The purpose of our investigation was to describe the immunological and pathological events that take place in the course of graft-versus-host disease (GVHD) and to gain insight into the cellular mechanisms underlying these events. To this end, a model was employed in which nonirradiated F1mice were used as recipients of parental lymphoid cells. By pathological manifestations, 2 basic forms of GVHD can be distinguished in such nonirradiated F1recipients: One is acute GVHD which is often lethal. It is characterized by a variety ofsuppressive (hypoplastic) pathological symptoms, including a severe hypoplasia of the lymphohemopoietic system accompanied by aplastic anemia and hypogammaglobulinemia. The other basic form is characterized bystimulatory symptoms, such as persistent lymphoid hyperplasia, formation of autoantibodies, and development of pathological symptoms reminiscent of SLE and other collagen vascular diseases. The suppressive pathological graft-versus-host (GVH) symptoms are caused by T suppressor/killer (TS/K) cells of the donor which react towards allogeneic class-I-structures of the F1recipient's major histocompatibility complex (MHC). The stimulatory pathological GVH symptoms, by contrast, are caused by donor T helper (TH) cells which react toward the recipient's allogeneic class-II-MHC structures.The possible implications of these observations for the pathogenesis of a number of GVH-like diseases in humans are discussed. The hypothesis is advanced that some of these GVH-like conditions, which arise eithere causa ignotaor after exposure to certain viruses or drugs, are caused by T lymphocytes reacting against self-MHC structures on lymphohemopoietic cells that were rendered “foreign”. By analogy to GVHD, it is conceivable that the development of either stimulatory or suppressive GHV-like symptoms in individuals exposed to a given virus or sensitizing drug depends not on the etiologic agend per se, but on whether the predeominant response is made by the individual's THorS/Kcells. This, in turn, might depend on whether the agent becomes immunogenic in combination with Class-II or class-I alloantigens.