Lehnert A M, Mottram P L, Han W, Walters S N, Patel A T, Hawthorne W J, Cowan P J, d'Apice A J, O'Connell P J
National Pancreas Transplant Unit, University of Sydney, Westmead Hospital, NSW, Australia.
Transpl Immunol. 2001 Oct;9(1):51-6. doi: 10.1016/s0966-3274(01)00040-5.
Previously, we demonstrated that combination CTLA4-Fc and anti-CD40L mAb treatment results in tolerance to concordant, cellular islet xenografts. The aim of this study was to determine its effectiveness in a model of fetal pig pancreas (FPP) xenotransplantation. Survival of FPP fragment grafts were compared to the survival of rat islet or cardiac xenografts following short term CTLA4-Fc and anti-CD40L mAb treatment. Rat islet and FPP fragment grafts survived long-term. However, rat cardiac grafts were rejected by 52-91 days. Both rat islet and FPP grafts showed similar histology with intact islet structures and adjacent 'nests' of lymphocytes. Concordant vascularised rat hearts showed extensive polymorphonuclear infiltrate, concentric vasculitis and a perivascular infiltrate predominantly of CD8+ T cells. This suggests that this therapy is effective for prolonging islet xenografts and demonstrates that the cellular mechanism of rejection for vascularised and non-vascularised xenografts are different.
此前，我们证明联合使用CTLA4-Fc和抗CD40L单克隆抗体治疗可诱导对协调性细胞胰岛异种移植物的耐受。本研究的目的是确定其在胎猪胰腺（FPP）异种移植模型中的有效性。将FPP片段移植物的存活情况与短期CTLA4-Fc和抗CD40L单克隆抗体治疗后的大鼠胰岛或心脏异种移植物的存活情况进行比较。大鼠胰岛和FPP片段移植物长期存活。然而，大鼠心脏移植物在52-91天被排斥。大鼠胰岛和FPP移植物均显示出相似的组织学特征，胰岛结构完整，淋巴细胞呈相邻“巢状”分布。协调性血管化大鼠心脏显示广泛的多形核浸润、同心性血管炎以及主要由CD8+T细胞组成的血管周围浸润。这表明该疗法对延长胰岛异种移植物的存活有效，并证明血管化和非血管化异种移植物的排斥细胞机制不同。
