Clonal analysis of murine graft-vs-host disease. I. Phenotypic and functional analysis of T lymphocyte clones.
Clonal analysis of murine graft-vs-host disease. I. Phenotypic and functional analysis of T lymphocyte clones.
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DOI：
10.4049/jimmunol.136.10.3543
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发表时间：
1986-05
影响因子：
4.4
通讯作者：
R. Parkman
中科院分区：
文献类型：
--
作者：
R. Parkman
急性和慢性移植物抗宿主病（GVHD）由于非MHC组织相容性差异的组织病理学不同。急性GVHD的特征在于受体组织的细胞毒性破坏，而慢性GVHD的特征在于胶原沉积增加。为了确定急性和慢性GVHD是否代表相同病理生理过程的两个阶段或两个不同的过程，已经克隆了来自LP脾细胞（非H-2 GVHD）的C57 BL/6（B6）受体的T淋巴细胞，并与来自免疫小鼠（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）克隆在移植后第50天从具有临床慢性GVHD的动物建立。免疫后10至14天建立免疫（I）克隆。所有I克隆均表现出B6特异性胚细胞发生和细胞毒性，并具有Thy-1.2+，Lyt-2.2+，L3 T4-表型。所有CG克隆均无细胞毒性，具有I-Ab特异性胚细胞发生，并具有Thy-1.2+、Lyt-2.2-、L3 T4+表型。急性GVHD（G）克隆具有异质性。23个克隆中有14个表现出B6特异性胚细胞发生，并具有Lyt-2.2+，L3 T4-表型（B6-G克隆）。9个B6-G克隆中有7个对B6靶标具有细胞毒性。23个G克隆中有9个表现出I-Ab特异性的胚细胞发生，除了一个克隆外，所有克隆都具有与CG克隆一样的Lyt-2.2-，L3 T4+表型。因此，来自患有急性和慢性GVHD的小鼠的主要克隆原性T淋巴细胞在1）它们的抗原特异性、2）它们的细胞毒性能力和3）它们的表面表型方面不同。移植后早期出现与CG克隆表型相同的I-Ab特异性T淋巴细胞表明导致慢性GVHD的免疫学事件在移植后不久开始。这些结果表明，急性GVHD主要是由于恶性特异性细胞毒性供体T淋巴细胞，而慢性GVHD是由于自身反应性辅助T淋巴细胞。
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.