IL-18 prevents the development of chronic graft-versus-host disease in mice
IL-18 prevents the development of chronic graft-versus-host disease in mice
复制标题
DOI：
10.4049/jimmunol.164.11.6067
复制
发表时间：
2000-06-01
影响因子：
4.4
通讯作者：
Kurimoto, M
中科院分区：
文献类型：
--
作者：
Okamoto, I;Kohno, K;Kurimoto, M
慢性移植物抗宿主病（GVHD）的发生是由DBA/2脾细胞转移到（C57BL/6 x DBA/2）F-1（BDF1）小鼠体内引起的，与供体抗宿主CTL活性降低和宿主B细胞过度活化密切相关。因此，激活供体CD8（+）T细胞或抑制供体CD4（+）T细胞与宿主B细胞相互作用的方法可能在治疗慢性移植物抗宿主病（GVHD）方面具有临床实用性。慢性GVHD，我们之前已经证明IL-18在DBA/2抗BDF1 MLC中诱导初始CD8(+)T细胞发育为I型效应细胞。在本文中，我们研究了 IL-18 给药对小鼠慢性 GVHD 发展的影响。治疗在疾病临床证据出现之前或之后开始。 ；无论治疗方案如何，IL-18 都会显着降低指示慢性 GVHD 的免疫学参数，例如血清 IgG 抗核抗体、IgG1 和 IgE 水平升高，以及宿主 B 细胞数量及其激活。重要的是，IL-18治疗的小鼠没有表现出与IL-12治疗相同的急性GVHD样症状，因为Con A刺激的脾细胞产生的IL-2和IFN-γ减少表明没有体重减轻、死亡或严重的免疫缺陷。相比之下，IL-18 治疗部分但显着恢复了这些细胞因子的产生。数据进一步表明，这些IL-18介导的治疗作用可能是由于供体CD8(+) CTL的诱导、供体CD4+ T细胞数量的减少以及宿主B细胞MHC II类表达的下调所致。因此，我们的结果表明IL-18在预防和治疗慢性GVHD方面具有有益作用。
The development of chronic graft-versus-host disease (GVHD), which is induced by the transfer of DBA/2 spleen cells into (C57BL/6 x DBA/2)F-1 (BDF1) mice, is closely related to diminished donor anti-host CTL activity and host B cell hyperactivation, Therefore, an approach which activates donor CD8(+) T cells or suppresses donor CD4(+) T cell-host B cell interaction may have clinical utility in the treatment of chronic GVHD, We have previously demonstrated that IL-18 induces the development of naive CD8(+) T cells into type I effector cells in DBA/2 anti-BDF1 MLC. In this paper we examined the effect of IL-18 administration on the development of chronic GVHD in mice. The treatment was started before or after the onset of clinical evidence of the disease. ;Regardless of the treatment schedule, IL-18 significantly decreased immunological parameters indicative of chronic GVHD, such as elevated serum IgG antinuclear Abs, IgG1, and IgE levels, and host B cell numbers and their activation. Importantly, IL-18-treated mice did not show the same acute GVHD-like symptoms reported for IL-12 treatment, because there was no weight loss, death, or severe immunodeficiency as indicated by a decrease in IL-2 and IFN-gamma production by Con A-stimulated spleen cells. In contrast, IL-18 treatment partially but significantly restored the production of these cytokines. Data further suggested that these IL-18-mediated therapeutic effects may be due to the induction of donor CD8(+) CTL, the decrease in donor CD4+ T cell numbers, and a down-regulation of host B cell MHC class II expression. Thus, our results suggest that IL-18 has beneficial effects in the prevention and treatment of chronic GVHD.