The role of tumor necrosis factor and interferon gamma in graft-versus-host disease and related immunodeficiency.
The role of tumor necrosis factor and interferon gamma in graft-versus-host disease and related immunodeficiency.
复制标题
DOI：
10.1097/00007890-199401001-00021
复制
发表时间：
1994
期刊：
影响因子：
6.2
通讯作者：
D. Wall;K. Sheehan
中科院分区：
文献类型：
--
作者：
D. Wall;K. Sheehan
在一个良好建立的小鼠GVHD模型中研究了TNF在GVHD和GVHD相关免疫缺陷表达中的作用，该模型是在体外和体内跨越次要组织相容性屏障（B10.BR-->GBA/J）进行骨髓移植的。来自GVHD动物的脾细胞以MHC非限制性方式对广泛的刺激作出反应，深刻地抑制正常脾细胞的增殖。中和TNF的mAb逆转了GVHD动物脾细胞抑制有丝分裂原伴刀豆球蛋白A刺激的正常脾细胞增殖的能力。rTNF的加入增强了抑制的程度。这种逆转类似于先前报道的IFN γ和亮氨酸甲酯治疗GVHD群体的逆转。所有这三种成分都是抑制发生所必需的，因为向抑制已被抗IFN γ或亮氨酸甲酯处理逆转的培养物中加入rTNF不会重建抑制。体内内源性TNF产生的中和导致临床GVHD的改善，但内源性IFN γ的中和导致更严重的过程。然而，在体内中和TNF或IFN γ后，BMT导致在一个降低的能力，脾细胞从动物GVHD抑制有丝分裂原反应，但不影响抑制细胞群的产生。这些发现支持TNF和IFN γ在GVHD的病理生理学中的多种作用，包括终末细胞分化和/或效应细胞功能的调节。
The role of TNF in the expression of GVHD and GVHD-related immunodeficiency was studied in a well-established murine GVHD model of bone marrow transplantation across minor histocompatibility barriers (B10.BR-->GBA/J) both in vitro and in vivo. Splenocytes from animals with GVHD profoundly inhibited the proliferation of normal spleen cells in response to a wide range of stimuli in an MHC-nonrestricted fashion. Neutralizing mAbs to TNF reversed the ability of splenocytes from animals with GVHD to suppress the proliferation of normal splenocytes stimulated by the mitogen concanavalin A. Addition of rTNF enhanced the degree of suppression. This reversal was similar to that previously reported for IFN gamma and leucine methyl ester treatment of the GVHD populations. All three components are necessary for suppression to occur because addition of rTNF to cultures in which suppression had been reversed by anti-IFN gamma or leucine methyl ester treatment did not reconstitute suppression. Neutralization of endogenous TNF production in vivo resulted in an amelioration of clinical GVHD, but neutralization of endogenous IFN gamma resulted in a more severe course. However, in vivo neutralization of either TNF or IFN gamma post-BMT resulted in a decreased ability of splenocytes from animals with GVHD to suppress mitogen responses but did not affect the generation of the suppressor cell population. These findings support multiple roles for TNF and IFN gamma in the pathophysiology of GVHD, including terminal cellular differentiation and/or regulation of effector cell function.