Orosz C G
Department of Surgery, Ohio State University College of Medicine, Columbus 43210, USA.
Clin Transplant. 1996 Feb;10(1 Pt 2):100-3.
We have observed that most C57BL/6 (H-2b) recipients of DBA/2 (H-2d) heterotopic cardiac allografts retain their grafts for more than 60 days following treatment with anti-CD4 MAb (GK1.5), anti-VCAM-1 MAb (M/K-2), or gallium nitrate (GN). Nevertheless, many ongoing alloimmune responses are detectable more than 60 d post-transplant in these mice: (i) continuous inflammatory endothelial activation and low-grade cellular infiltration in the graft, (ii) modest frequencies of donor-reactive T cells in the graft and spleen, (iii) mRNA for various cytokines (IL-1, IL-2, IL-4, IL-6, IFN gamma, TNF alpha, TGF beta) in the graft, (iv) high levels of donor-reactive alloantibody in the circulation, (v) variable development of allogeneic chimerism in the recipient, and (vi) development of interstitial fibrosis and neointimal hyperplasia in the graft. Despite the widely differing targets of GK1.5, M/K-2, and GN, their therapeutic outcomes appear to be identical. Taken together, these observations suggest that long-term allograft survival in these experimental systems is not the result of immune acceptance, i.e. allogeneic tolerance. Although these therapies interrupt the destructive progression of acute rejection, they permit many related immune responses in the graft recipient in association with the development of chronic rejection-like histopathology.
我们观察到，在用抗CD4单克隆抗体（GK1.5）、抗VCAM-1单克隆抗体（M/K-2）或硝酸镓（GN）治疗后，大多数接受DBA/2（H-2d）异位心脏同种异体移植的C57BL/6（H-2b）受体的移植物可保留60天以上。然而，在这些小鼠移植后60天以上仍可检测到许多持续的同种免疫反应：（i）移植物中持续的炎症性内皮激活和低度细胞浸润；（ii）移植物和脾脏中供体反应性T细胞的频率适中；（iii）移植物中各种细胞因子（IL-1、IL-2、IL-4、IL-6、IFNγ、TNFα、TGFβ）的mRNA；（iv）循环中高水平的供体反应性同种抗体；（v）受体中同种异体嵌合体的不同程度发展；（vi）移植物中间质纤维化和新内膜增生的发展。尽管GK1.5、M/K-2和GN的靶点差异很大，但它们的治疗结果似乎相同。综上所述，这些观察结果表明，在这些实验系统中，长期同种异体移植存活并非免疫接受即同种异体耐受的结果。虽然这些疗法中断了急性排斥的破坏性进展，但它们允许移植受体中许多相关的免疫反应与慢性排斥样组织病理学的发展相关联。
