Induction of immunological tolerance by cell adhesion moleculerelated substances.

本研究的目的是生成可溶形式的细胞粘附分子，可以有效地抑制T细胞活化和增殖的共刺激信号。我们生成了一种融合蛋白，由人IgG_1或人IgM的Fc部分和小鼠CTLA4的细胞外部分（分别为CTLA4- igg和CTLA4-IgM）组成。与CTLA4-IgG相比，CTLA4-IgM能有效抑制混合淋巴细胞反应（MLR）诱导的T细胞增殖。此外，低浓度FK506和CTLA4-IgM （2.3mug/ml）联合使用可显著延长同种异体心脏移植存活率（C57BL/6至CBA/J），而FK506 + CTLA4-IgG （2.3mug/ml）联合使用可适度延长移植物存活率。

The purpose of this study was to generate soluble forms of cell adhesion molecules which can efficiently inhibit the costimulatory signals for T cell activation and proliferation. We generated a fusion protein consisting of a Fc portion of human IgG_1 or human IgM and an extracellular portion of mouse CTLA4 (CTLA4-IgG and CTLA4-IgM,respectively).CTLA4-IgM efficiently inhibited the T cell proliferation induced by mixed lymphocyte reaction (MLR) as compared to CTLA4-IgG.Furthermore, the combination of low does FK506 and CTLA4-IgM (2.3mug/ml) resulted in significant prolongation of cardiac allograft surviral (C57BL/6 into CBA/J), where as cardiac alloglaft surviral in recipients treated with FK506 plus CTLA4-IgG (2.3mug/ml) resulted in moderate prolongation of grafts.