Interferon-gamma deficiency prevents coronary arteriosclerosis but not myocardial rejection in transplanted mouse hearts
Interferon-gamma deficiency prevents coronary arteriosclerosis but not myocardial rejection in transplanted mouse hearts
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DOI：
10.1172/jci119564
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发表时间：
1997-08-01
影响因子：
15.9
通讯作者：
Libby, P
中科院分区：
文献类型：
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作者：
Nagano, H;Mitchell, RN;Libby, P
我们假设T细胞因子参与移植物动脉疾病（GAD）的发病机制。本研究测试了ifn - γ缺乏对小鼠同种异体心脏移植的动脉和病理的影响，将来自C-H-2(bm12)KhEg （bm12, H-2(bm12)）的心脏移植到C57/B6 (B6, H-2(b))，野生型或B6 ifn - γ缺乏（GKO）的受体中，在抗cd4和抗cd8单克隆抗体治疗免疫抑制后，野生型受体心肌排斥反应在第4周达到顶峰，（评分2.1+/-0.3 / 4，平均+/-SEM， n = 9）， 8-12周演变为冠状动脉病变。12周时，GAD评分为1.4+/-0.3，实质排斥反应等级为1.2+/-0.3 （n = 8）。在bm12同种异体移植GKO受体中，心肌排斥反应持续至12周（2.5+/-0.3级，n = 6），但未发生GAD（评分：0.0+/-0.0,n = 6，与野生型相比P < 0.01）。用抗ifn - γ单抗治疗的小鼠也显示出类似的结果，同种移植物一般没有出现动脉改变。与正常或等移植的心脏相比，动脉和实质细胞的MHCⅱ类分子、细胞间黏附分子-1和血管细胞黏附分子-1增加，GKO受体的同种异体移植物显示这些分子的表达减弱（n = 6），因此，GAD的发生，而不是实质排斥，需要ifn - γ。MHC抗原和白细胞粘附分子的表达降低可能导致同种异体移植到GKO小鼠的心脏中没有冠状动脉病变。
We have hypothesized that T cell cytokines participate in the pathogenesis of graft arterial disease (GAD). This study tested the consequences of IFN-gamma, deficiency on arterial and parenchymal pathology in murine cardiac allografts, Hearts from C-H-2(bm12)KhEg (bm12, H-2(bm12)) were transplanted into C57/B6 (B6, H-2(b)), wild-type, or B6 IFN-gamma-deficient (GKO) recipients after immunosuppression by treatment with anti-CD4 and anti-CD8 mAbs, In wild-type recipients, myocardial rejection peaked at 4 wk, (grade 2.1+/-0.3 out of 4, mean+/-SEM, n = 9), and by 8-12 wk evolved coronary arteriopathy. At 12 wk, the GAD score was 1.4+/-0.3, and the parenchymal rejection grade was 1.2+/-0.3 (n = 8), In GKO recipients of bm12 allografts, myocardial rejection persisted at 12 wk (grade 2.5+/-0.3, n = 6), but no GAD developed (score: 0.0+/-0.0, n = 6, P < 0.01 vs. wild-type). Mice treated with anti-IFN-gamma mAbs showed similar results, Isografts generally showed no arterial changes, In wild-type recipients? arterial and parenchymal cells showed increased MHC class II molecules, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 compared to normal or isografted hearts, The allografts in GKO recipients showed attenuated expression of these molecules (n = 6), Thus, development of GAD, but not parenchymal rejection, requires IFN-gamma. Reduced expression of MHC antigens and leukocyte adhesion molecules may contribute to the lack of coronary arteriopathy in hearts allografted into GKO mice.