Jerome K R, Conyers S J, Hansen D A, Zebala J A
Department of Laboratory Medicine, University of Washington, Seattle 98195, USA.
Bone Marrow Transplant. 1998 Aug;22(4):359-66. doi: 10.1038/sj.bmt.1701344.
Acute graft-versus-host disease (GVHD) is a complication of bone marrow transplantation (BMT). The histopathologic features used to diagnose GVHD are nonspecific, and may be secondary to chemotherapy or irradiation given before BMT. The presence of apoptotic keratinocytes or activated CTL may distinguish GVHD from conditioning effects. This study investigated the relationship in BMT recipients between keratinocyte apoptosis and the effects of conditioning regimens or immune-mediated GVHD. Inflammatory cells, apoptotic keratinocytes, and CTL expressing TIA-1 (a molecule associated with the lytic granules of CTL) were quantitated in allogeneic and autologous recipients. Allogeneic recipients could exhibit keratinocyte apoptosis secondary to a combination of conditioning effects and immune-mediated GVHD. In contrast, autologous recipients should show conditioning effects only. 'Capped' TIA-1-positive lymphocytes and apoptotic keratinocytes were much more frequent in the allogeneic group than the autologous group (16.1% of total TIA-1 positive lymphocytes vs 4.5%, P=0.02; and 37.6/mm2 vs 3.9/mm2, P = 0.005, respectively), although there was some overlap in their frequency. Among individual recipients of allogeneic BMT, the number of epidermal lymphocytes or macrophages correlated with the number of apoptotic keratinocytes. A similar, but weaker, correlation was seen between the number of 'capped' TIA-1-positive lymphocytes and apoptotic keratinocytes. No such relationship was seen in autologous recipients. In allogeneic recipients, TIA-1 expressing CTL were seen in intimate contact with apoptotic keratinocytes, some of which also had detectable cytoplasmic TIA-1. No CTL/keratinocyte interactions were identified in autologous recipients. Our results suggest that apoptotic keratinocytes arise in the skin of BMT patients due to both GVHD and conditioning effects, and that the keratinocyte damage in GVHD is mediated by both CTL-dependent and -independent mechanisms. Increased numbers of apoptotic keratinocytes, in the presence of increased epidermal lymphocytes or 'capped' TIA-l-expressing lymphocytes, support a diagnosis of GVHD, but must be interpreted in the context of clinical information and other histopathologic findings.
急性移植物抗宿主病（GVHD）是骨髓移植（BMT）的一种并发症。用于诊断GVHD的组织病理学特征是非特异性的，可能继发于BMT前给予的化疗或放疗。凋亡角质形成细胞或活化的细胞毒性T淋巴细胞（CTL）的存在可将GVHD与预处理效应区分开来。本研究调查了BMT受者中角质形成细胞凋亡与预处理方案的效应或免疫介导的GVHD之间的关系。对异基因和自体受者中的炎性细胞、凋亡角质形成细胞以及表达TIA-1（一种与CTL的溶细胞颗粒相关的分子）的CTL进行了定量分析。异基因受者可能会由于预处理效应和免疫介导的GVHD共同作用而出现角质形成细胞凋亡。相比之下，自体受者应该仅表现出预处理效应。在异基因组中，“帽状”TIA-1阳性淋巴细胞和凋亡角质形成细胞比自体组更为常见（分别占TIA-1阳性淋巴细胞总数的16.1%和4.5%，P = 0.02；以及37.6/mm²和3.9/mm²，P = 0.005），尽管它们的频率存在一定重叠。在异基因BMT个体受者中，表皮淋巴细胞或巨噬细胞的数量与凋亡角质形成细胞的数量相关。在“帽状”TIA-1阳性淋巴细胞数量与凋亡角质形成细胞数量之间也观察到了类似但较弱的相关性。在自体受者中未观察到这种关系。在异基因受者中，可见表达TIA-1的CTL与凋亡角质形成细胞紧密接触，其中一些凋亡角质形成细胞的细胞质中也可检测到TIA-1。在自体受者中未发现CTL/角质形成细胞相互作用。我们的结果表明，BMT患者皮肤中的凋亡角质形成细胞是由GVHD和预处理效应共同导致的，并且GVHD中角质形成细胞的损伤是由CTL依赖性和非依赖性机制介导的。在表皮淋巴细胞或“帽状”表达TIA-1的淋巴细胞数量增加的情况下，凋亡角质形成细胞数量增加支持GVHD的诊断，但必须结合临床信息和其他组织病理学发现进行解释。
