Ghayur T, Seemayer T A, Xenocostas A, Lapp W S
Department of Physiology, McGill University, Montreal, Canada.
Am J Pathol. 1988 Oct;133(1):39-46.
This study presents the sequential morphologic regeneration of graft-vs.-host (GVH)-induced dysplastic thymuses in long-term survivors of GVH reactions. GVH reactions were induced in adult C57BL/6xAF1 (B6AF1) hybrids by injecting 20 x 10(6) A strain parental lymphoid cells (PLC). Starting on day 30 after GVH induction, five to ten animals were randomly selected from a pool of GVH-reactive mice and killed at various times. Each animal was tested for thymic histology and T cell functions. Thymuses taken on day 30 after GVH induction displayed severe dysplasia as characterized by lymphocytic depletion, complete effacement of cortico-medullary demarcation, and reduction and total loss of medullary epithelial cells or both. Starting by days 60-70 after GVH induction, at least four stages of thymic regeneration were identified. Day 60-70 thymuses displayed cortical regeneration and the reappearance of cortico-medullary demarcation. The medulla of these thymuses, although containing dark individual epithelial cells and numerous lymphocytes, was devoid of pale epithelial cells (stage 1). The medulla of thymuses on day 100 after GVH induction displayed a few sparcely distributed pale epithelial cells and numerous lymphocytes as well as dark epithelial cells (stage 2). The medulla of thymuses examined 130 days after GVH induction displayed numerous pale individual epithelial cells and a few pale epithelial cell clusters. Such thymuses also showed a reduction in the number of medullary lymphocytes (stage 3). Finally, the medulla of thymuses 150-160 days after GVH induction displayed numerous pale epithelial cell clusters and Hassall's bodies. These thymuses were indistinguishable from normal adult thymuses (stage 4). All of the animals tested up to day 130 after GVH induction showed no significant T cell function. Animals displaying stage 4 of thymic regeneration showed significant proliferative responses to T cell mitogen, concanavalin A (conA), and six of ten animals also displayed a few plaque forming cells (PFC) to sheep red blood cells (SRBC) in their spleens. Furthermore, all animals (10 of 10) killed on day 180 after GVH induction displayed significant T cell functions.(ABSTRACT TRUNCATED AT 400 WORDS)
本研究展示了移植物抗宿主（GVH）反应长期存活者中，GVH诱导的发育异常胸腺的序贯形态学再生。通过注射20×10⁶个A系亲代淋巴细胞（PLC），在成年C57BL/6×AF1（B6AF1）杂交小鼠中诱导GVH反应。在GVH诱导后第30天开始，从一组GVH反应性小鼠中随机选取5至10只动物，并在不同时间处死。对每只动物进行胸腺组织学和T细胞功能检测。GVH诱导后第30天取出的胸腺显示出严重发育异常，其特征为淋巴细胞耗竭、皮质-髓质分界完全消失、髓质上皮细胞减少或完全缺失，或两者皆有。从GVH诱导后第60 - 70天开始，至少确定了胸腺再生的四个阶段。第60 - 70天的胸腺显示皮质再生以及皮质-髓质分界重新出现。这些胸腺的髓质虽然含有深色的单个上皮细胞和大量淋巴细胞，但缺乏浅色上皮细胞（阶段1）。GVH诱导后第100天胸腺的髓质显示有少量稀疏分布的浅色上皮细胞、大量淋巴细胞以及深色上皮细胞（阶段2）。GVH诱导后130天检查的胸腺髓质显示有大量浅色单个上皮细胞和少量浅色上皮细胞簇。此类胸腺的髓质淋巴细胞数量也有所减少（阶段3）。最后，GVH诱导后150 - 160天胸腺的髓质显示有大量浅色上皮细胞簇和哈氏小体。这些胸腺与正常成年胸腺无法区分（阶段4）。在GVH诱导后第130天之前检测的所有动物均未显示出明显的T细胞功能。显示胸腺再生阶段4的动物对T细胞有丝分裂原刀豆球蛋白A（conA）表现出显著的增殖反应，并且10只动物中有6只在其脾脏中对绵羊红细胞（SRBC）也显示出一些空斑形成细胞（PFC）。此外，在GVH诱导后第180天处死的所有动物（10只中的10只）均显示出明显的T细胞功能。（摘要截断于400字）
