Parkman R
J Immunol. 1986 May 15;136(10):3543-8.
Acute and chronic graft-vs-host disease (GVHD) due to non-MHC histocompatibility differences differ histopathologically. Acute GVHD is characterized by the cytotoxic destruction of recipient tissues, whereas chronic GVHD is characterized by increased collagen deposition. In an attempt to determine if acute and chronic GVHD represent two phases of the same pathophysiologic process or two distinct processes, the T lymphocytes from the C57BL/6 (B6) recipients of LP spleen cells (non-H-2 GVHD) have been cloned and compared to clones from immune mice (LP anti-B6). Acute GVHD (G) clones were established on day 10-14 posttransplant and chronic GVHD (CG) clones on day 50 from animals with clinical chronic GVHD. Immune (I) clones were established 10 to 14 days after immunization. All I clones exhibited B6-specific blastogenesis and cytotoxicity and had a Thy-1.2+, Lyt-2.2+, L3T4- phenotype. All CG clones were noncytotoxic, had I-Ab-specific blastogenesis, and had a Thy-1.2+, Lyt-2.2-, L3T4+ phenotype. The acute GVHD (G) clones were heterogeneous. Fourteen of 23 clones exhibited B6-specific blastogenesis and had a Lyt-2.2+, L3T4- phenotype (B6-G clones). Seven of 9 B6-G clones were cytotoxic for B6 targets. Nine of 23 G clones exhibited I-Ab-specific blastogenesis, and all but one clone had a Lyt-2.2-, L3T4+ phenotype as the did CG clones. Thus, the principal clonogenic T lymphocytes from mice with acute and chronic GVHD differ in terms of 1) their antigenic specificity, 2) their cytotoxic capacity, and 3) their surface phenotype. The presence of I-Ab-specific T lymphocytes with a phenotype identical to CG clones early after transplantation suggests that the immunologic events that result in chronic GVHD begin soon after transplantation. These results indicate that acute GVHD is due primarily to recipient-specific cytotoxic donor T lymphocytes, whereas chronic GVHD is due to autoreactive helper T lymphocytes.
由非主要组织相容性复合体（MHC）组织相容性差异引起的急性和慢性移植物抗宿主病（GVHD）在组织病理学上有所不同。急性GVHD的特征是受体组织的细胞毒性破坏，而慢性GVHD的特征是胶原蛋白沉积增加。为了确定急性和慢性GVHD是代表同一病理生理过程的两个阶段还是两个不同的过程，对接受LP脾细胞的C57BL/6（B6）受体（非H-2 GVHD）的T淋巴细胞进行了克隆，并与免疫小鼠（LP抗B6）的克隆进行了比较。急性GVHD（G）克隆在移植后第10 - 14天建立，慢性GVHD（CG）克隆在临床慢性GVHD动物的第50天建立。免疫（I）克隆在免疫后10至14天建立。所有I克隆均表现出B6特异性母细胞生成和细胞毒性，且具有Thy-1.2 +、Lyt-2.2 +、L3T4 - 表型。所有CG克隆均无细胞毒性，具有I-Ab特异性母细胞生成，且具有Thy-1.2 +、Lyt-2.2 -、L3T4 + 表型。急性GVHD（G）克隆具有异质性。23个克隆中的14个表现出B6特异性母细胞生成，且具有Lyt-2.2 +、L3T4 - 表型（B6-G克隆）。9个B6-G克隆中的7个对B6靶细胞具有细胞毒性。23个G克隆中的9个表现出I-Ab特异性母细胞生成，除1个克隆外，所有克隆均具有与CG克隆相同的Lyt-2.2 -、L3T4 + 表型。因此，来自急性和慢性GVHD小鼠的主要克隆形成性T淋巴细胞在以下方面存在差异：1）它们的抗原特异性，2）它们的细胞毒性能力，3）它们的表面表型。移植后早期存在表型与CG克隆相同的I-Ab特异性T淋巴细胞，这表明导致慢性GVHD的免疫事件在移植后不久就开始了。这些结果表明，急性GVHD主要归因于受体特异性细胞毒性供体T淋巴细胞，而慢性GVHD归因于自身反应性辅助性T淋巴细胞。
