Involvement of Interleukin-18 in Acute Graft-Versus-Host Disease in Mice
Involvement of Interleukin-18 in Acute Graft-Versus-Host Disease in Mice
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DOI：
10.1097/01.tp.0000137934.25190.b9
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发表时间：
2004-11
期刊：
影响因子：
6.2
通讯作者：
H. Itoi;Y. Fujimori;H. Tsutsui;K. Matsui;A. Sugihara;N. Terada;T. Hada;E. Kakishita;H. Okamura;H. Hara;K. Nakanishi
中科院分区：
文献类型：
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作者：
H. Itoi;Y. Fujimori;H. Tsutsui;K. Matsui;A. Sugihara;N. Terada;T. Hada;E. Kakishita;H. Okamura;H. Hara;K. Nakanishi
背景白细胞介素（IL）-18刺激辅助性T细胞1（Th 1）介导的免疫应答和细胞毒性T淋巴细胞（CTL）的发展。抗宿主CTL是急性移植物抗宿主病（aGvHD）的主要效应物，aGvHD是异基因干细胞移植后的潜在致命并发症。我们研究了IL-18在小鼠aGvHD发展中的相关作用。方法.将移植野生型（WT）C57 BL/6（B6）脾细胞的辐照（C57 BL/6× DBA/2）F1（BDF 1）小鼠与移植IL-18 R缺陷型B6脾细胞的小鼠在Th 1发育、CTL活性、aGvHD严重程度和存活率方面进行比较。结果将WT B6脾细胞移植到BDF 1小鼠中诱导aGvHD，其伴随着血清IL-18水平和移植T细胞上的IL-18受体链（IL-18 R）表达的升高。WT B6细胞的移植也在宿主脾中诱导高的抗宿主CTL活性，而IL-18 R缺陷型B6细胞的移植表现出显著降低的抗宿主特异性CTL活性，表明IL-18 R缺陷型CTL的细胞毒性低于表达IL-18 R的CTL。此外，与接受WT细胞移植的宿主相比，接受IL-18 R缺陷型B6细胞移植的宿主具有较少的致命组织损伤，并且提高了它们的存活率。然而，无论供体细胞类型如何，宿主中的Th 1发育都是相同的。结论.这些结果表明，在aGvHD中，Th 1诱导和基线CTL活性在不存在IL-18的情况下发生，但内源性IL-18进一步加速aGvHD反应至其完全表现。因此，IL-18可能通过增强CTL活性参与aGvHD的发展。
Background. Interleukin (IL)-18 stimulates T helper 1 (Th1)-mediated immune responses and the development of cytotoxic T lymphocytes (CTLs). Antihost CTLs are major effectors in acute graft-versus-host disease (aGvHD), a potentially fatal complication after allogeneic stem-cell transplantation. We investigated the relevant role of IL-18 in the development of aGvHD in mice. Methods. Irradiated (C57BL/6× DBA/2) F1 (BDF1) mice transplanted with wild-type (WT) C57BL/6 (B6) splenocytes were compared with those transplanted with IL–18R-deficient B6 splenocytes with respect to Th1 development, CTL activity, severity of aGvHD, and survival. Results. Transplantation of WT B6 spleen cells into BDF1 mice induced aGvHD that was accompanied by elevation of both serum IL-18 levels and IL-18 receptor chain (IL-18R) expression on engrafted T cells. The transplantation of WT B6 cells also induced high antihost CTL activity in host spleen, whereas transplantation of IL–18R-deficient B6 cells exhibited significantly reduced antihost-specific CTL activity, indicating that IL–18R-deficient CTLs were less cytotoxic than IL–18R-expressing CTLs. Moreover, the hosts receiving transplants with the IL–18R-deficient B6 cells had fewer fatal tissue injuries and increased their survival rates as compared with those receiving transplants with WT cells. Nevertheless, Th1 development in the hosts was the same, regardless of the type of donor cells. Conclusions. These results suggest that Th1 induction and baseline CTL activity in aGvHD occur in the absence of IL-18, but endogenous IL-18 further accelerates aGvHD reaction to its full-blown manifestation. Thus, IL-18 may be involved in the development aGvHD by enhancing CTL activity.