Gorczynski R M, Cattral M S, Chen Z, Hu J, Lei J, Min W P, Yu G, Ni J
Transplant Research Division, The Toronto Hospital, Canada.
J Immunol. 1999 Aug 1;163(3):1654-60.
We have established that, in mice receiving donor-specific immunization by the portal vein, the increased graft survival seen is associated with the increased expression of a molecule (OX-2) on a subpopulation of dendritic cells (DC), and polarization of cytokine production to type 2 cytokines on Ag-specific restimulation of cells from these mice. Furthermore, infusion of a mAb to OX-2 blocks both the increased graft survival and the altered cytokine production seen. We have constructed an immunoadhesin in which the extracellular domain of OX-2 is linked to the murine IgG2a Fc region, and we have expressed this molecule (OX-2:Fc) in a eukaryotic (baculovirus) expression system. Incubation of lymphocytes with 50 ng/ml OX-2:Fc inhibits a primary mixed lymphocyte reaction in vitro, as assayed by proliferation and induction of cytotoxic T cells, and also alters cytokine production with decreased IL-2 (IFN-gamma) production and increased IL-4 (IL-10) production. Similarly, in vivo infusion of OX-2:Fc promotes increased allo- and xenograft (both skin and renal grafts) survival and decreases the Ab response to sheep erythrocytes. Our data suggest this molecule might have clinical importance in allo- and xenotransplantation.
我们已经证实，在通过门静脉接受供体特异性免疫的小鼠中，观察到的移植存活率提高与树突状细胞（DC）亚群上一种分子（OX-2）的表达增加有关，并且在对这些小鼠的细胞进行抗原特异性再刺激时，细胞因子产生向2型细胞因子极化。此外，注入抗OX-2单克隆抗体可阻断观察到的移植存活率提高和细胞因子产生改变。我们构建了一种免疫粘附素，其中OX-2的细胞外结构域与小鼠IgG2a Fc区域相连，并且我们已经在真核（杆状病毒）表达系统中表达了该分子（OX-2:Fc）。用50 ng/ml OX-2:Fc孵育淋巴细胞可在体外抑制初次混合淋巴细胞反应，通过增殖和细胞毒性T细胞诱导进行测定，并且还会改变细胞因子产生，降低IL-2（IFN-γ）产生并增加IL-4（IL-10）产生。同样，在体内注入OX-2:Fc可促进同种异体和异种移植（皮肤和肾移植）存活率提高，并降低对绵羊红细胞的抗体反应。我们的数据表明该分子可能在同种异体和异种移植中具有临床重要性。
