Fujita T, Matsumoto Y, Hirai I, Ezoe K, Saito T, Yagihashi A, Torigoe T, Homma K, Takahashi S, Cruikshank W W, Jimbow K, Sato N
Division of Plastic Surgery, Sapporo Medical University School of Medicine, Sapporo, 060-8543, Japan.
Cell Immunol. 2000 May 25;202(1):54-60. doi: 10.1006/cimm.2000.1657.
It is well known that it is difficult to induce an immunotolerance with allogeneic skin transplantation. We attempted to find the immunosuppressive protocol for prolonging skin allograft rejection by using interleukin-16 because IL-16 is considered one of the natural ligands to CD4 molecules. First we examined whether synergistic immunosuppressive effects of recombinant IL-16 plus anti-CD4 mAbs are induced in mixed lymphocyte reaction (MLR). Next we used IL-16-cDNA-transfected OSC-20 (human oral squamous cell carcinoma cell line) as an in vitro model of the epidermal keratinocyte equivalent and examined whether this transfectant could inhibit the activation of allogeneic T cells. Our data indicated that IL-16 clearly inhibited human MLR and that IL-16 increased synergistically the immunosuppressive effect of anti-CD4 mAb. We also used IL-16 transfectant and this produced more than 50 ng/ml of IL-16 in the supernatant by which human MLR was significantly inhibited. Furthermore, this transfectant also inhibited the activation of allogeneic lymphocytes stimulated directly with transfectant cells. These results indicated that the IL-16-producing allogeneic skin graft might have a local immunosuppressive action that would prolong graft survival.
众所周知,通过同种异体皮肤移植诱导免疫耐受是困难的。我们试图通过使用白细胞介素-16来寻找延长皮肤同种异体移植排斥反应的免疫抑制方案,因为白细胞介素-16被认为是CD4分子的天然配体之一。首先,我们研究了在混合淋巴细胞反应(MLR)中是否能诱导重组白细胞介素-16加抗CD4单克隆抗体的协同免疫抑制作用。接下来,我们使用转染了白细胞介素-16 cDNA的OSC-20(人口腔鳞状细胞癌细胞系)作为表皮角质形成细胞等效物的体外模型,并研究这种转染细胞是否能抑制同种异体T细胞的活化。我们的数据表明,白细胞介素-16能明显抑制人混合淋巴细胞反应,并且白细胞介素-16能协同增强抗CD4单克隆抗体的免疫抑制作用。我们还使用了白细胞介素-16转染细胞,其在上清液中产生了超过50 ng/ml的白细胞介素-16,人混合淋巴细胞反应因此受到显著抑制。此外,这种转染细胞还抑制了由转染细胞直接刺激的同种异体淋巴细胞的活化。这些结果表明,产生白细胞介素-16 的同种异体皮肤移植物可能具有局部免疫抑制作用,从而延长移植物存活时间。