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外源性白细胞介素-10在小鼠次要组织相容性抗原移植物抗宿主病模型中的作用

Effects of exogenous interleukin-10 in a murine model of graft-versus-host disease to minor histocompatibility antigens.

作者信息

Krenger W, Snyder K, Smith S, Ferrara J L

机构信息

Department of Pediatric Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115.

出版信息

Transplantation. 1994 Dec 15;58(11):1251-7.

PMID:7992370
Abstract

IL-10 is a regulatory cytokine of both T cells and monocytes. We have investigated the ability of IL-10 to regulate responses to alloantigens in vitro and in vivo. Addition of IL-10 to mixed lymphocyte cultures profoundly decreased the proliferation and IL-2 production by donor B10.BR cells stimulated with CBA cells expressing minor histocompatibility antigens. Administration of IL-10 for a period of 2 weeks after bone marrow transplantation decreased the expansion of CD4+ and CD8+ donor T cells. In addition, splenocytes from BMT mice treated with IL-10 secreted less IFN-gamma after stimulation with Con A in vitro. The suppression of the mitogen-driven proliferative response of lymphocytes from the IL-10-treated group could also be reversed with significantly less anti-IFN-gamma antibody than for saline-treated controls. However, treatment with IL-10 was not sufficient to alter significantly the clinical course of graft-versus-host disease in CBA recipient mice as assessed by survival, weight loss, and splenomegaly. The results suggest that exogenous IL-10 suppresses the afferent Th1 response in a graft-versus-host reaction but does not significantly diminish the effector stage of graft-versus-host disease.

摘要

白细胞介素-10是一种对T细胞和单核细胞均有调节作用的细胞因子。我们研究了白细胞介素-10在体外和体内调节同种异体抗原反应的能力。向混合淋巴细胞培养物中添加白细胞介素-10,可显著降低表达次要组织相容性抗原的CBA细胞刺激的供体B10.BR细胞的增殖及白细胞介素-2的产生。骨髓移植后给予白细胞介素-10 2周,可减少CD4⁺和CD8⁺供体T细胞的扩增。此外,用白细胞介素-10处理的骨髓移植小鼠的脾细胞在体外经刀豆蛋白A刺激后分泌的γ干扰素较少。与盐水处理的对照组相比,用明显较少的抗γ干扰素抗体即可逆转白细胞介素-10处理组淋巴细胞有丝分裂原驱动的增殖反应的抑制。然而,通过生存、体重减轻和脾肿大评估,白细胞介素-10治疗不足以显著改变CBA受体小鼠移植物抗宿主病的临床病程。结果表明,外源性白细胞介素-10在移植物抗宿主反应中抑制传入性Th1反应,但不会显著减轻移植物抗宿主病的效应阶段。

相似文献

1
Effects of exogenous interleukin-10 in a murine model of graft-versus-host disease to minor histocompatibility antigens.外源性白细胞介素-10在小鼠次要组织相容性抗原移植物抗宿主病模型中的作用
Transplantation. 1994 Dec 15;58(11):1251-7.
2
A CD8 DE loop peptide analog prevents graft-versus-host disease in a multiple minor histocompatibility antigen-mismatched bone marrow transplantation model.一种CD8 DE环肽类似物在多微小组织相容性抗原不匹配的骨髓移植模型中可预防移植物抗宿主病。
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3
Selective elimination of alloreactive donor T cells attenuates graft-versus-host disease and enhances T-cell reconstitution.选择性清除同种异体反应性供体T细胞可减轻移植物抗宿主病并增强T细胞重建。
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Alleviation of chronic GVHD in mice by oral immuneregulation toward recipient pretransplant splenocytes does not jeopardize the graft versus leukemia effect.通过对受体移植前脾细胞进行口服免疫调节来减轻小鼠慢性移植物抗宿主病,不会损害移植物抗白血病效应。
Hum Immunol. 2005 Mar;66(3):231-40. doi: 10.1016/j.humimm.2004.12.004.
5
Graft-facilitating doses of ex vivo activated gammadelta T cells do not cause lethal murine graft-vs.-host disease.体外激活的γδT细胞的移植物促进剂量不会引发致死性小鼠移植物抗宿主病。
Biol Blood Marrow Transplant. 1999;5(4):222-30. doi: 10.1053/bbmt.1999.v5.pm10465102.
6
Prevention of graft-versus-host disease by a novel immunosuppressant, (5R)-5-hydroxytriptolide (LLDT-8), through expansion of regulatory T cells.新型免疫抑制剂(5R)-5-羟基雷公藤内酯醇(LLDT-8)通过扩增调节性T细胞预防移植物抗宿主病
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7
IL-7 drives donor T cell proliferation and can costimulate cytokine secretion after MHC-matched allogeneic bone marrow transplantation.白细胞介素-7可驱动供体T细胞增殖,并在MHC匹配的异基因骨髓移植后共刺激细胞因子分泌。
J Immunol. 1995 Jan 1;154(1):106-15.
8
Ex vivo anti-CD3 antibody-activated donor T cells have a reduced ability to cause lethal murine graft-versus-host disease but retain their ability to facilitate alloengraftment.体外抗CD3抗体激活的供体T细胞导致致死性小鼠移植物抗宿主病的能力降低,但仍保留其促进同种异体移植的能力。
J Immunol. 1998 Sep 1;161(5):2610-9.
9
Donor antigen-presenting cells regulate T-cell expansion and antitumor activity after allogeneic bone marrow transplantation.供体抗原呈递细胞在异基因骨髓移植后调节T细胞扩增和抗肿瘤活性。
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10
Co-stimulated/Tc2 cells abrogate murine marrow graft rejection.共刺激/Tc2细胞消除小鼠骨髓移植排斥反应。
Biol Blood Marrow Transplant. 2004 Sep;10(9):604-13. doi: 10.1016/j.bbmt.2004.06.006.

引用本文的文献

1
Influence of pro- and anti-inflammatory cytokines in Th1 polarization after allogeneic stimulation.促炎细胞因子和抗炎细胞因子在同种异体刺激后Th1极化中的作用。
Int J Biomed Sci. 2005 Jun;1(1):46-52.
2
Separating graft-versus-leukemia from graft-versus-host disease in allogeneic hematopoietic stem cell transplantation.在异基因造血干细胞移植中,区分移植物抗白血病与移植物抗宿主病。
Immunotherapy. 2009 Jul;1(4):599-621. doi: 10.2217/imt.09.32.
3
Th2 cell therapy of established acute graft-versus-host disease requires IL-4 and IL-10 and is abrogated by IL-2 or host-type antigen-presenting cells.
已确诊的急性移植物抗宿主病的Th2细胞疗法需要白细胞介素-4和白细胞介素-10,并且会被白细胞介素-2或宿主型抗原呈递细胞所消除。
Biol Blood Marrow Transplant. 2008 Sep;14(9):959-972. doi: 10.1016/j.bbmt.2008.06.007.
4
Interleukin-18 regulates acute graft-versus-host disease by enhancing Fas-mediated donor T cell apoptosis.白细胞介素-18通过增强Fas介导的供体T细胞凋亡来调节急性移植物抗宿主病。
J Exp Med. 2001 Nov 19;194(10):1433-40. doi: 10.1084/jem.194.10.1433.
5
Th1 and Th2 mediate acute graft-versus-host disease, each with distinct end-organ targets.Th1和Th2介导急性移植物抗宿主病,各自具有不同的终末器官靶点。
J Clin Invest. 2000 May;105(9):1289-98. doi: 10.1172/JCI7894.
6
Donor-derived interferon gamma is required for inhibition of acute graft-versus-host disease by interleukin 12.供体来源的干扰素γ是白细胞介素12抑制急性移植物抗宿主病所必需的。
J Clin Invest. 1998 Dec 15;102(12):2126-35. doi: 10.1172/JCI4992.
7
Differential effects of the absence of interferon-gamma and IL-4 in acute graft-versus-host disease after allogeneic bone marrow transplantation in mice.小鼠同种异体骨髓移植后急性移植物抗宿主病中干扰素-γ和白细胞介素-4缺失的不同作用
J Clin Invest. 1998 Nov 1;102(9):1742-8. doi: 10.1172/JCI3906.
8
Graft-versus-host disease and the Th1/Th2 paradigm.移植物抗宿主病与Th1/Th2范式
Immunol Res. 1996;15(1):50-73. doi: 10.1007/BF02918284.