Zand M S, Li Y, Hancock W, Li X C, Roy-Chaudhury P, Zheng X X, Strom T B
Division of Immunology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA.
Transplantation. 2000 Nov 15;70(9):1378-81. doi: 10.1097/00007890-200011150-00019.
Several studies suggest that MHC-mismatched allografts reject with a Th1 or Th2 immune response, but these models all have low-level expression of the Th1 cytokines interleukin (IL)-2 and interferon-gamma (IFN-gamma).
We interbred mice with single targeted gene disruptions for IL-2 and IFN-gamma to establish IL-2 + IFN-gamma double knockout (DKO) mice. Heterotopic cardiac allografts from DBA/2j (H2d) donors were transplanted WT, IL-2 knockout (KO), IFN-gamma KO, and DKO recipients (C57BL/6x129; H2b). Cytokine transcripts from allografts and DKO splenocytes were analyzed by reverse transcription polymerase chain reaction.
DKO mice had a cytokine profile and IgG1/ IgG2a isotype ratio characteristic of Th2 deviation. DKO recipients rejected heterotopic cardiac allografts faster than IL-2 KO mice, but significantly slower than WT and IFN-gamma KO mice (P<0.01). Analysis of the rejecting DKO recipients showed intragraft Th2 cytokine expression.
The combined absence of IL-2 and IFN-gamma in the setting of Th2 deviation does not prevent allograft rejection.
多项研究表明，主要组织相容性复合体（MHC）不匹配的同种异体移植物会通过Th1或Th2免疫反应发生排斥，但这些模型中Th1细胞因子白细胞介素（IL）-2和干扰素-γ（IFN-γ）的表达水平均较低。
我们将针对IL-2和IFN-γ的单基因敲除小鼠进行杂交，以建立IL-2 + IFN-γ双敲除（DKO）小鼠。将来自DBA/2j（H2d）供体的异位心脏同种异体移植物移植到野生型、IL-2敲除（KO）、IFN-γ KO和DKO受体（C57BL/6x129；H2b）体内。通过逆转录聚合酶链反应分析同种异体移植物和DKO脾细胞中的细胞因子转录本。
DKO小鼠具有Th2偏移特征性的细胞因子谱和IgG1/IgG2a同种型比率。DKO受体排斥异位心脏同种异体移植物的速度比IL-2 KO小鼠快，但明显慢于野生型和IFN-γ KO小鼠（P<0.01）。对正在发生排斥的DKO受体的分析显示移植物内有Th2细胞因子表达。
在Th2偏移的情况下，IL-2和IFN-γ同时缺失并不能阻止同种异体移植物的排斥。
