Donor-derived interferon γ separates graft-versus-leukemia effects and graft-versus-host disease induced by donor CD8 T cells
Donor-derived interferon γ separates graft-versus-leukemia effects and graft-versus-host disease induced by donor CD8 T cells
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DOI：
10.1182/blood.v99.11.4207
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发表时间：
2002-06-01
期刊：
影响因子：
20.3
通讯作者：
Sykes, M
中科院分区：
文献类型：
--
作者：
Yang, YG;Qi, J;Sykes, M
在野生型（WT）或干扰素γ (ifn - γ)缺陷（GKO）同种异体供体细胞的小鼠受体中，比较了CD8 T细胞的移植物抗白血病（GVL）效应和移植物抗宿主病（GVHD）诱导活性。与来自WT供体的相同细胞群相比，来自GKO供体小鼠的CD8 T细胞（或cd4缺失的脾细胞）在致命照射的同种异体受体中诱导更严重的GVHD。与GVHD的严重程度一致，在缺乏ifn - γ的情况下，供体CD8 t细胞在异体受体中扩增。这些结果表明ifn - γ不刺激而是下调供体CD8 T细胞诱导的GVHD。值得注意的是，CD8 T细胞的抗宿主淋巴造血反应，包括GVL对宿主白血病/淋巴瘤细胞的作用，与其诱导gvhd的活性呈负相关，并且GKO供者的抗宿主淋巴造血反应明显弱于WT供者CD8 T细胞介导的抗宿主淋巴造血反应。这些数据首次表明，同种异体CD8 T细胞的gvhd诱导活性和GVL效应可以通过单一细胞因子ifn - γ分离。(C) 2002年由美国血液病学会出版。
The graft-versus-leukemia (GVL) effects and graft-versus-host disease (GVHD)-inducing activity of CD8 T cells was compared in murine recipients of wild-type (WT) or interferon gamma (IFN-gamma)-deficient (GKO) allogeneic donor cells. CD8 T cells (or CD4-depleted splenocytes) from GKO donor mice induced more severe GVHD in lethally irradiated allogeneic recipients compared to the same cell populations from WT donors. Consistent with GVHD severity, donor CD8 T-cell expansion in allogeneic recipients was augmented in the absence of IFN-gamma. These results demonstrate that IFN-gamma does not stimulate but instead down-modulates GVHD induced by donor CD8 T cells. Remarkably, anti-host lymphohematopoietic reactions, including GVL effects against host leukemia/lymphoma cells, of CD8 T cells correlated inversely with their GVHD-inducing activity, and those of GKO donors were markedly weaker than those mediated by WT donor CD8 T cells. These data show for the first time that GVHD-inducing activity and GVL effects of allogeneic CD8 T cells can be separated by a single cytokine, IFN-gamma. (C) 2002 by The American Society of Hematology.